The Enzyme Database: New Enzymes

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Nomenclature Committee of the International Union of Biochemistry and Molecular Biology (NC-IUBMB)

Proposed Changes to the Enzyme List

The entries below are proposed additions and amendments to the Enzyme Nomenclature list. They were prepared for the NC-
IUBMB by Keith Tipton, Sinéad Boyce, Gerry Moss and Hal Dixon, with occasional help from other Committee members, and were
put on the web by Gerry Moss. Comments and suggestions on these draft entries should be sent to

Professor K.F. Tipton and Dr S.

Boyce

(Department of Biochemistry, Trinity College Dublin, Dublin 2, Ireland) by 20 May 2006, after which, the entries will be made

official and will be incorporated into the main enzyme list. To prevent confusion please do not quote new EC numbers until they are
incorporated into the main list.

Many thanks to those of you who have submitted details of new enzymes or updates to existing enzymes.

An asterisk before 'EC' indicates that this is an amendment to an existing enzyme rather than a new enzyme entry.

Contents

*EC 1.1.1.262

4-hydroxythreonine-4-phosphate dehydrogenase

EC 1.1.1.289

sorbose reductase

EC 1.1.1.290

4-phosphoerythronate dehydogenase

EC 1.1.99.19 transferred

*EC 1.2.1.10

acetaldehyde dehydrogenase (acetylating)

EC 1.2.1.71

succinylglutamate-semialdehyde dehydrogenase

EC 1.2.1.72

erythrose-4-phosphate dehydrogenase

EC 1.2.99.1 transferred

*EC 1.3.99.19

quinoline-4-carboxylate 2-oxidoreductase

*EC 1.4.3.5

pyridoxal 5′-phosphate synthase

*EC 1.4.4.2

glycine dehydrogenase (decarboxylating)

EC 1.7.1.13

queuine synthase

*EC 1.8.1.4

dihydrolipoyl dehydrogenase

*EC 1.11.1.14

lignin peroxidase

EC 1.11.1.16

versatile peroxidase

*EC 1.13.11.11

tryptophan 2,3-dioxygenase

*EC 1.13.11.19

cysteamine dioxygenase

EC 1.13.11.42 deleted

EC 1.13.11.52

indoleamine 2,3-dioxygenase

EC 1.13.11.53

acireductone dioxygenase (Ni

-requiring)

EC 1.13.11.54

acireductone dioxygenase [iron(II)-requiring]

EC 1.13.11.55

sulfur oxygenase/reductase

EC 1.13.12.14

chlorophyllide-

oxygenase

EC 1.14.13.65 deleted

EC 1.14.13.101

senecionine

-oxygenase

*EC 1.14.99.3

heme oxygenase

EC 1.17.99.4

uracil/thymine dehydrogenase

*EC 2.1.2.10

aminomethyltransferase

*EC 2.3.1.11

thioethanolamine

-acetyltransferase

*EC 2.3.1.38

[acyl-carrier-protein]

-acetyltransferase

*EC 2.3.1.39

[acyl-carrier-protein]

-malonyltransferase

*EC 2.3.1.41

β-ketoacyl-acyl-carrier-protein synthase I

*EC 2.3.1.109

arginine

-succinyltransferase

EC 2.3.1.177

biphenyl synthase

EC 2.3.1.178

diaminobutyrate acetyltransferase

EC 2.3.1.179

β-ketoacyl-acyl-carrier-protein synthase II

EC 2.3.1.180

β-ketoacyl-acyl-carrier-protein synthase III

EC 2.3.1.181

lipoyl(octanoyl) transferase

*EC 2.4.1.195

-hydroxythioamide

-β-glucosyltransferase

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EC 2.4.1.243

-fructosyltransferase

EC 2.4.1.244

-acetyl-β-glucosaminyl-glycoprotein 4-β-

-acetylgalactosaminyltransferase

*EC 2.6.1.52

phosphoserine transaminase

*EC 2.6.1.76

diaminobutyrate—2-oxoglutarate transaminase

EC 2.6.1.81

succinylornithine transaminase

EC 2.6.99.2

pyridoxine 5′-phosphate synthase

*EC 2.7.1.151

inositol-polyphosphate multikinase

EC 2.7.1.158

inositol-pentakisphosphate 2-kinase

EC 2.7.1.159

inositol-1,3,4-trisphosphate 5/6-kinase

EC 2.7.4.22

UMP kinase

EC 2.7.7.63

lipoate—protein ligase

*EC 2.8.1.6

biotin synthase

EC 2.8.1.8

lipoyl synthase

EC 3.1.3.76

lipid-phosphate phosphatase

EC 3.1.13.5

ribonuclease D

*EC 3.1.26.3

ribonuclease III

*EC 3.2.1.81

β-agarase

*EC 3.2.1.83

κ-carrageenase

EC 3.2.1.155

xyloglucan-specific exo-β-1,4-glucanase

EC 3.2.1.157

ι-carrageenase

EC 3.2.1.158

α-agarase

EC 3.2.1.159

α-neoagaro-oligosaccharide hydrolase

EC 3.2.1.161

β-apiosyl-β-glucosidase

EC 3.3.2.3 transferred

*EC 3.3.2.6

leukotriene-A

hydrolase

*EC 3.3.2.7

hepoxilin-epoxide hydrolase

EC 3.3.2.9

microsomal epoxide hydrolase

EC 3.3.2.10

soluble epoxide hydrolase

EC 3.3.2.11

cholesterol-5,6-oxide hydrolase

EC 3.4.21.87 transferred

EC 3.4.23.49

omptin

EC 3.5.1.94

γ-glutamyl-γ-aminobutyrate hydrolase

EC 3.5.1.95

-malonylurea hydrolase

EC 3.5.1.96

succinylglutamate desuccinylase

*EC 3.5.2.1

barbiturase

EC 3.5.3.23

-succinylarginine dihydrolase

*EC 3.6.3.5

-exporting ATPase

*EC 3.6.3.44

xenobiotic-transporting ATPase

EC 3.6.3.45 deleted

*EC 4.1.1.21

phosphoribosylaminoimidazole carboxylase

EC 4.1.1.86

diaminobutyrate decarboxylase

*EC 4.1.2.8

indole-3-glycerol-phosphate lyase

EC 4.1.3.39

4-hydroxy-2-oxovalerate aldolase

*EC 4.2.1.60

3-hydroxydecanoyl-[acyl-carrier-protein] dehydratase

EC 4.2.1.108

ectoine synthase

*EC 4.2.3.9

aristolochene synthase

EC 4.2.3.22

germacradienol synthase

EC 4.2.3.23

germacrene-A synthase

EC 4.2.3.24

amorpha-4,11-diene synthase

EC 4.2.3.25

-linalool synthase

EC 4.2.3.26

-linalool synthase

EC 4.4.1.24

sulfolactate sulfo-lyase

EC 4.4.1.25

-cysteate sulfo-lyase

EC 5.3.3.14

trans

-2-decenoyl-[acyl-carrier protein] isomerase

EC 5.4.99.18

5-(carboxyamino)imidazole ribonucleotide mutase

*EC 6.3.2.6

phosphoribosylaminoimidazolesuccinocarboxamide synthase

*EC 6.3.2.27

aerobactin synthase

EC 6.3.4.18

5-(carboxyamino)imidazole ribonucleotide synthase

*EC 1.1.1.262

Common name: 4-hydroxythreonine-4-phosphate dehydrogenase

Reaction: 4-(phosphonooxy)-

-threonine + NAD

= (2

)-2-amino-3-oxo-4-phosphonooxybutanoate + NADH

+ H

For diagram of pyridoxal biosynthesis,

click here

Other name(s): NAD

-dependent threonine 4-phosphate dehydrogenase;

-threonine 4-phosphate dehydrogenase;

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4-(phosphohydroxy)-

-threonine dehydrogenase; PdxA

Systematic name: 4-(phosphonooxy)-

-threonine:NAD

oxidoreductase

Comments: The product of the reaction undergoes decarboxylation to give 3-amino-2-oxopropyl phosphate. In

Escherichia coli

, the coenzyme pyridoxal 5′-phosphate is synthesized de novo by a pathway that

involves

EC 1.2.1.72

(erythrose-4-phosphate dehydrogenase),

EC 1.1.1.290

(4-

phosphoerythronate dehydrogenase),

EC 2.6.1.52

(phosphoserine transaminase), EC 1.1.1.262 (4-

hydroxythreonine-4-phosphate dehydrogenase),

EC 2.6.99.2

(pyridoxine 5′-phosphate synthase)

and

EC 1.4.3.5

(with pyridoxine 5′-phosphate as substrate).

Links to other databases:

BRENDA

ERGO

EXPASY

IUBMB

KEGG

PDB

References: 1. Cane, D.E., Hsiung, Y., Cornish, J.A., Robinson, J.K and Spenser, I.D. Biosynthesis of vitamine

: The oxidation of

-threonine 4-phosphate by PdxA.

J. Am. Chem. Soc.

120 (1998) 1936–

1937.

2. Laber, B., Maurer, W., Scharf, S., Stepusin, K. and Schmidt, F.S. Vitamin B

biosynthesis:

formation of pyridoxine 5′-phosphate from 4-(phosphohydroxy)-

-threonine and 1-deoxy-

xylulose-5-phosphate by PdxA and PdxJ protein.

FEBS Lett.

449 (1999) 45–48. [PMID:

10225425

]

3. Sivaraman, J., Li, Y., Banks, J., Cane, D.E., Matte, A. and Cygler, M. Crystal structure of

Escherichia coli

PdxA, an enzyme involved in the pyridoxal phosphate biosynthesis pathway.

Biol. Chem.

278 (2003) 43682–43690. [PMID:

12896974

]

[EC 1.1.1.262 created 2000, modified 2006]

EC 1.1.1.289

Common name: sorbose reductase

Reaction:

-glucitol + NADP

-sorbose + NADPH + H

For diagram of reaction,

click here

Glossary:

-sorbose =

xylo

-hex-2-ulose

Other name(s): Sou1p

Systematic name:

-glucitol:NADP

oxidoreductase

Comments: The reaction occurs predominantly in the reverse direction. This enzyme can also convert

fructose into

-mannitol, but more slowly. Belongs in the short-chain dehydrogenase family.

References: 1. Greenberg, J.R., Price, N.P., Oliver, R.P., Sherman, F. and Rustchenko, E.

Candida albicans

SOU1

encodes a sorbose reductase required for

-sorbose utilization.

Yeast

22 (2005) 957–969.

[PMID:

16134116

]

2. Greenberg, J.R., Price, N.P., Oliver, R.P., Sherman, F. and Rustchenko, E. Erratum report:

Candida albicans

SOU1 encodes a sorbose reductase required for

-sorbose utilization.

Yeast

(2005) 1171 only.

3. Sugisawa, T., Hoshino, T. and Fujiwara, A. Purification and properties of NADPH-linked

sorbose reductase from

Gluconobacter melanogenus

N44-1.

Agric. Biol. Chem.

55 (1991) 2043–

2049.

4. Shinjoh, M., Tazoe, M. and Hoshino, T. NADPH-dependent

-sorbose reductase is responsible

for

-sorbose assimilation in

Gluconobacter suboxydans

IFO 3291.

J. Bacteriol.

184 (2002) 861–

863. [PMID:

11790761

]

[EC 1.1.1.289 created 2006]

EC 1.1.1.290

Common name: 4-phosphoerythronate dehydogenase

Reaction: 4-phospho-

-erythronate + NAD

= (3

)-3-hydroxy-2-oxo-4-phosphonooxybutanoate + NADH +

For diagram of pyridoxal biosynthesis,

click here

Other name(s): PdxB; PdxB 4PE dehydrogenase; 4-

-phosphoerythronate dehydrogenase

Systematic name: 4-phospho-

-erythronate:NAD

2-oxidoreductase

Comments: This enzyme catalyses the second step in the biosynthesis of the coenzyme pyridoxal 5′-phosphate

Escherichia coli

. The reaction occurs predominantly in the reverse direction [3]. Other enzymes

involved in this pathway are

EC 1.2.1.72

(erythrose-4-phosphate dehydrogenase),

EC 2.6.1.52

(phosphoserine transaminase),

EC 1.1.1.262

(4-hydroxythreonine-4-phosphate dehydrogenase),

EC 2.6.99.2

(pyridoxine 5′-phosphate synthase) and

EC 1.4.3.5

(pyridoxamine-phosphate oxidase).

References: 1. Lam, H.M. and Winkler, M.E. Metabolic relationships between pyridoxine (vitamin B

) and serine

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biosynthesis in

Escherichia coli

K-12.

J. Bacteriol.

172 (1990) 6518–6528. [PMID:

2121717

]

2. Pease, A.J., Roa, B.R., Luo, W. and Winkler, M.E. Positive growth rate-dependent regulation of

the

pdxA

ksgA

, and

pdxB

genes of

Escherichia coli

K-12.

J. Bacteriol.

184 (2002) 1359–1369.

[PMID:

11844765

]

3. Zhao, G. and Winkler, M.E. A novel α-ketoglutarate reductase activity of the

serA

-encoded 3-

phosphoglycerate dehydrogenase of

Escherichia coli

K-12 and its possible implications for

human 2-hydroxyglutaric aciduria.

J. Bacteriol.

178 (1996) 232–239. [PMID:

8550422

]

4. Grant, G.A. A new family of 2-hydroxyacid dehydrogenases.

Biochem. Biophys. Res. Commun.

165 (1989) 1371–1374. [PMID:

2692566

]

5. Schoenlein, P.V., Roa, B.B. and Winkler, M.E. Divergent transcription of

pdxB

and homology

between the

pdxB

and

serA

gene products in

Escherichia coli

K-12.

J. Bacteriol.

171 (1989)

6084–6092. [PMID:

2681152

]

[EC 1.1.1.290 created 2006]

EC 1.1.99.19

Transferred entry: uracil dehydrogenase. Now

EC 1.17.99.4

, uracil/thymine dehydrogenase

[EC 1.1.99.19 created 1961 as EC 1.2.99.1, transferred 1984 to EC 1.1.99.19, deleted 2006]

*EC 1.2.1.10

Common name: acetaldehyde dehydrogenase (acetylating)

Reaction: acetaldehyde + CoA + NAD

= acetyl-CoA + NADH + H

Other name(s): aldehyde dehydrogenase (acylating); ADA; acylating acetaldehyde dehyrogenase; DmpF

Systematic name: acetaldehyde:NAD

oxidoreductase (CoA-acetylating)

Comments: Also acts, more slowly, on glycolaldehyde, propanal and butanal. In

Pseudomonas

species, this

enzyme forms part of a bifunctional enzyme with

EC 4.1.3.39

, 4-hydroxy-2-oxovalerate aldolase. It

is the final enzyme in the meta-cleavage pathway for the degradation of phenols, cresols and
catechol, converting the acetaldehyde produced by

EC 4.1.3.39

into acetyl-CoA [3]. NADP

can

replace NAD

but the rate of reaction is much slower [3].

Links to other databases:

BRENDA

ERGO

EXPASY

GTD

IUBMB

KEGG

, CAS registry number: 9028-91-5

References: 1. Burton, R.M. and Stadtman, E.R. The oxidation of acetaldehyde to acetyl coenzyme A.

J. Biol.

Chem.

202 (1953) 873–890. [PMID:

13061511

]

2. Smith, L.T. and Kaplan, N.O. Purification, properties, and kinetic mechanism of coenzyme A-

linked aldehyde dehydrogenase from

Clostridium kluyveri

Arch. Biochem. Biophys.

203 (1980)

663–675. [PMID:

7458347

]

3. Powlowski, J., Sahlman, L. and Shingler, V. Purification and properties of the physically

associated meta-cleavage pathway enzymes 4-hydroxy-2-ketovalerate aldolase and aldehyde
dehydrogenase (acylating) from

Pseudomonas

sp. strain CF600.

J. Bacteriol.

175 (1993) 377–

385. [PMID:

8419288

]

[EC 1.2.1.10 created 1961, modified 2006]

EC 1.2.1.71

Common name: succinylglutamate-semialdehyde dehydrogenase

Reaction:

-succinyl-

-glutamate 5-semialdehyde + NAD

+ H

O =

-succinyl-

-glutamate + NADH + 2 H

For diagram of arginine catabolism,

click here

Other name(s): succinylglutamic semialdehyde dehydrogenase;

-succinylglutamate 5-semialdehyde

dehydrogenase; SGSD; AruD; AstD

Systematic name:

-succinyl-

-glutamate 5-semialdehyde:NAD

oxidoreductase

Comments: This is the fourth enzyme in the arginine succinyltransferase (AST) pathway for the catabolism of

arginine [1]. This pathway converts the carbon skeleton of arginine into glutamate, with the
concomitant production of ammonia and conversion of succinyl-CoA into succinate and CoA. The
five enzymes involved in this pathway are

EC 2.3.1.109

(arginine

-succinyltransferase),

3.5.3.23

(

-succinylarginine dihydrolase),

EC 2.6.1.11

(acetylornithine transaminase), EC 1.2.1.71

(succinylglutamate-semialdehyde dehydrogenase) and

EC 3.5.1.96

(succinylglutamate

desuccinylase) [3,6].

References: 1. Vander Wauven, C., Jann, A., Haas, D., Leisinger, T. and Stalon, V.

-succinylornithine in

ornithine catabolism of

Pseudomonas aeruginosa

Arch. Microbiol.

150 (1988) 400–404. [PMID:

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3144259

]

2. Vander Wauven, C. and Stalon, V. Occurrence of succinyl derivatives in the catabolism of

arginine in

Pseudomonas cepacia

J. Bacteriol.

164 (1985) 882–886. [PMID:

2865249

]

3. Tricot, C., Vander Wauven, C., Wattiez, R., Falmagne, P. and Stalon, V. Purification and

properties of a succinyltransferase from

Pseudomonas aeruginosa

specific for both arginine and

ornithine.

Eur. J. Biochem.

224 (1994) 853–861. [PMID:

7523119

]

4. Itoh, Y. Cloning and characterization of the

aru

genes encoding enzymes of the catabolic

arginine succinyltransferase pathway in

Pseudomonas aeruginosa

J. Bacteriol.

179 (1997)

7280–7290. [PMID:

9393691

]

5. Schneider, B.L., Kiupakis, A.K. and Reitzer, L.J. Arginine catabolism and the arginine

succinyltransferase pathway in

Escherichia coli

J. Bacteriol.

180 (1998) 4278–4286. [PMID:

9696779

]

6. Cunin, R., Glansdorff, N., Pierard, A. and Stalon, V. Biosynthesis and metabolism of arginine in

bacteria.

Microbiol. Rev.

50 (1986) 314–352. [PMID:

3534538

]

7. Cunin, R., Glansdorff, N., Pierard, A. and Stalon, V. Erratum report: Biosynthesis and

metabolism of arginine in bacteria.

Microbiol. Rev.

51 (1987) 178 only.

[EC 1.2.1.71 created 2006]

EC 1.2.1.72

Common name: erythrose-4-phosphate dehydrogenase

Reaction:

-erythrose 4-phosphate + NAD

+ H

O = 4-phosphoerythronate + NADH + 2 H

For diagram of pyridoxal biosynthesis,

click here

Other name(s): erythrose 4-phosphate dehydrogenase; E4PDH; GapB; Epd dehydrogenase; E4P dehydrogenase

Systematic name:

-erythrose 4-phosphate:NAD

oxidoreductase

Comments: This enzyme was originally thought to be a glyceraldehyde-3-phosphate dehydrogenase (

1.2.1.12

), but this has since been disproved, as glyceraldehyde 3-phosphate is not a substrate

[1,2]. Forms part of the pyridoxal-5′-phosphate coenzyme biosynthesis pathway in

Escherichia coli

along with

EC 1.1.1.290

(4-phosphoerythronate dehydrogenase),

EC 2.6.1.52

(phosphoserine

transaminase),

EC 1.1.1.262

(4-hydroxythreonine-4-phosphate dehydrogenase),

EC 2.6.99.2

(pyridoxine 5′-phosphate synthase) and

EC 1.4.3.5

(pyridoxamine-phosphate oxidase).

References: 1. Zhao, G., Pease, A.J., Bharani, N. and Winkler, M.E. Biochemical characterization of gapB-

encoded erythrose 4-phosphate dehydrogenase of

Escherichia coli

K-12 and its possible role in

pyridoxal 5′-phosphate biosynthesis.

J. Bacteriol.

177 (1995) 2804–2812. [PMID:

7751290

]

2. Boschi-Muller, S., Azza, S., Pollastro, D., Corbier, C. and Branlant, G. Comparative enzymatic

properties of GapB-encoded erythrose-4-phosphate dehydrogenase of

Escherichia coli

and

phosphorylating glyceraldehyde-3-phosphate dehydrogenase.

J. Biol. Chem.

272 (1997) 15106–

15112. [PMID:

9182530

]

3. Yang, Y., Zhao, G., Man, T.K. and Winkler, M.E. Involvement of the

gapA

- and

epd

(

gapB

encoded dehydrogenases in pyridoxal 5′-phosphate coenzyme biosynthesis in

Escherichia coli

K-12.

J. Bacteriol.

180 (1998) 4294–4299. [PMID:

9696782

]

[EC 1.2.1.72 created 2006]

EC 1.2.99.1

Transferred entry: now

EC 1.17.99.4

, uracil/thymine dehydrogenase

[EC 1.2.99.1 created 1961, deleted 1984]

*EC 1.3.99.19

Common name: quinoline-4-carboxylate 2-oxidoreductase

Reaction: quinoline-4-carboxylate + acceptor + H

O = 2-oxo-1,2-dihydroquinoline-4-carboxylate + reduced

acceptor

For diagram of reaction,

click here

Other name(s): quinaldic acid 4-oxidoreductase; quinoline-4-carboxylate:acceptor 2-oxidoreductase (hydroxylating)

Systematic name: quinoline-4-carboxylate:acceptor 2-oxidoreductase (hydroxylating)

Comments: A molybdenum—iron—sulfur flavoprotein with molybdopterin cytosine dinucleotide as the

molybdenum cofactor. Quinoline, 4-methylquinoline and 4-chloroquinoline can also serve as
substrates for the enzyme from

Agrobacterium

sp. 1B. Iodonitrotetrazolium chloride, thionine,

menadione and 2,6-dichlorophenolindophenol can act as electron acceptors.

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Links to other databases:

BRENDA

ERGO

EXPASY

IUBMB

KEGG

, CAS registry number: 175780-18-4

References: 1. Bauer, G. and Lingens, F. Microbial metabolism of quinoline and related compounds. XV.

Quinoline-4-carboxylic acid oxidoreductase from

Agrobacterium

spec.1B: a molybdenum-

containing enzyme.

Biol. Chem. Hoppe-Seyler

373 (1992) 699–705. [PMID:

1418685

]

[EC 1.3.99.19 created 1999, modified 2006]

*EC 1.4.3.5

Common name: pyridoxal 5′-phosphate synthase

Reaction: (1) pyridoxamine 5′-phosphate + H

O + O

= pyridoxal 5′-phosphate + NH

+ H

(2) pyridoxine 5′-phosphate + O

= pyridoxal 5′-phosphate + H

For diagram of pyridoxal biosynthesis,

click here

Other name(s): pyridoxamine 5′-phosphate oxidase; pyridoxamine phosphate oxidase; pyridoxine

(pyridoxamine)phosphate oxidase; pyridoxine (pyridoxamine) 5′-phosphate oxidase;
pyridoxaminephosphate oxidase (EC 1.4.3.5: deaminating); PMP oxidase; pyridoxol-5′-
phosphate:oxygen oxidoreductase (deaminating) (incorrect); pyridoxamine-phosphate oxidase;
PdxH

Systematic name: pyridoxamine-5′-phosphate:oxygen oxidoreductase (deaminating)

Comments: A flavoprotein (FMN). In

Escherichia coli

, the coenzyme pyridoxal 5′-phosphate is synthesized de

novo by a pathway that involves

EC 1.2.1.72

(erythrose-4-phosphate dehydrogenase),

1.1.1.290

(4-phosphoerythronate dehydrogenase),

EC 2.6.1.52

(phosphoserine transaminase),

1.1.1.262

(4-hydroxythreonine-4-phosphate dehydrogenase),

EC 2.6.99.2

(pyridoxine 5′-phosphate

synthase) and EC 1.4.3.5 (with pyridoxine 5′-phosphate as substrate).

Links to other databases:

BRENDA

ERGO

EXPASY

IUBMB

KEGG

PDB

, CAS registry number: 9029-21-4

References: 1. Choi, J.-D., Bowers-Komro, D.M., Davis, M.D., Edmondson, D.E. and McCormick, D.B. Kinetic

properties of pyridoxamine (pyridoxine)-5′-phosphate oxidase from rabbit liver.

J. Biol. Chem.

258 (1983) 840–845. [PMID:

6822512

]

2. Wada, H. and Snell, E.E. The enzymatic oxidation of pyridoxine and pyridoxamine phosphates.

J. Biol. Chem.

236 (1961) 2089–2095. [PMID:

13782387

]

3. Notheis, C., Drewke, C. and Leistner, E. Purification and characterization of the pyridoxol-5′-

phosphate:oxygen oxidoreductase (deaminating) from

Escherichia coli

Biochim. Biophys. Acta

1247 (1995) 265–271. [PMID:

7696318

]

4. Laber, B., Maurer, W., Scharf, S., Stepusin, K. and Schmidt, F.S. Vitamin B

biosynthesis:

formation of pyridoxine 5′-phosphate from 4-(phosphohydroxy)-

-threonine and 1-deoxy-

xylulose-5-phosphate by PdxA and PdxJ protein.

FEBS Lett.

449 (1999) 45–48. [PMID:

10225425

]

5. Musayev, F.N., Di Salvo, M.L., Ko, T.P., Schirch, V. and Safo, M.K. Structure and properties of

recombinant human pyridoxine 5′-phosphate oxidase.

Protein Sci.

12 (2003) 1455–1463. [PMID:

12824491

]

6. Safo, M.K., Musayev, F.N. and Schirch, V. Structure of

Escherichia coli

pyridoxine 5′-phosphate

oxidase in a tetragonal crystal form: insights into the mechanistic pathway of the enzyme.

Acta

Crystallogr. D Biol. Crystallogr.

61 (2005) 599–604. [PMID:

15858270

]

[EC 1.4.3.5 created 1961, modified 2006]

*EC 1.4.4.2

Common name: glycine dehydrogenase (decarboxylating)

Reaction: glycine + H-protein-lipoyllysine = H-protein-

-aminomethyldihydrolipoyllysine + CO

For diagram of the glycine cleavage system,

click here

Glossary:

dihydrolipoyl group

Other name(s): P-protein; glycine decarboxylase; glycine-cleavage complex; glycine:lipoylprotein oxidoreductase

(decarboxylating and acceptor-aminomethylating); protein P1

Systematic name: glycine:H-protein-lipoyllysine oxidoreductase (decarboxylating, acceptor-amino-methylating)

Comments: A pyridoxal-phosphate protein. A component, with

EC 2.1.2.10

, aminomethyltransferase and

1.8.1.4

, dihydrolipoyl dehydrogenanse, of the glycine cleavage system, previously known as glycine

synthase. The glycine cleavage system is composed of four components that only loosely
associate: the P protein (EC 1.4.4.2), the T protein (

EC 2.1.2.10

), the L protein (

EC 1.8.1.4

) and the

lipoyl-bearing H protein [3].

Links to other databases:

BRENDA

ERGO

EXPASY

IUBMB

KEGG

, CAS registry number: 37259-67-9

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http://www.enzyme-database.org/newenz.php?sp=off

References: 1. Hiraga, K. and Kikuchi, G. The mitochondrial glycine cleavage system. Functional association of

glycine decarboxylase and aminomethyl carrier protein.

J. Biol. Chem.

255 (1980) 11671–11676.

[PMID:

7440563

]

2. Perham, R.N. Swinging arms and swinging domains in multifunctional enzymes: catalytic

machines for multistep reactions.

Annu. Rev. Biochem.

69 (2000) 961–1004. [PMID:

10966480

]

3. Nesbitt, N.M., Baleanu-Gogonea, C., Cicchillo, R.M., Goodson, K., Iwig, D.F., Broadwater, J.A.,

Haas, J.A., Fox, B.G. and Booker, S.J. Expression, purification, and physical characterization of

Escherichia coli

lipoyl(octanoyl)transferase.

Protein Expr. Purif.

39 (2005) 269–282. [PMID:

15642479

]

[EC 1.4.4.2 created 1984, modified 2003, modified 2006]

EC 1.7.1.13

Common name: queuine synthase

Reaction: queuine + 2 NADP

= 7-cyano-7-carbaguanine + 2 NADPH + 2 H

For diagram of reaction,

click here

Glossary: queuine = 7-aminomethyl-7-carbaguanine = preQ

Other name(s): YkvM; QueF; preQ

reductase; preQ

oxidoreductase; 7-cyano-7-deazaguanine reductase; 7-

aminomethyl-7-carbaguanine:NADP

oxidoreductase

Systematic name: queuine:NADP

oxidoreductase

Comments: The reaction occurs in the reverse direction. This enzyme catalyses one of the early steps in the

synthesis of queosine (Q-tRNA), and is followed by the action of

EC 2.4.2.29

, queuine tRNA-

ribosyltransferase. Queosine is found in the wobble position of tRNA

GUN

in Eukarya and Bacteria

[2] and is thought to be involved in translational modulation. The enzyme is not a GTP
cyclohydrolase, as was thought previously based on sequence-homology studies.

References: 1. Van Lanen, S.G., Reader, J.S., Swairjo, M.A., de Crécy-Lagard, V., Lee, B. and Iwata-Reuyl, D.

From cyclohydrolase to oxidoreductase: discovery of nitrile reductase activity in a common fold.

Proc. Natl. Acad. Sci. USA

102 (2005) 4264–4269. [PMID:

15767583

]

2. Yokoyama, S., Miyazawa, T., Iitaka, Y., Yamaizumi, Z., Kasai, H. and Nishimura, S. Three-

dimensional structure of hyper-modified nucleoside Q located in the wobbling position of tRNA.

Nature

282 (1979) 107–109. [PMID:

388227

]

3. Kuchino, Y., Kasai, H., Nihei, K. and Nishimura, S. Biosynthesis of the modified nucleoside Q in

transfer RNA.

Nucleic Acids Res.

3 (1976) 393–398. [PMID:

1257053

]

4. Okada, N., Noguchi, S., Nishimura, S., Ohgi, T., Goto, T., Crain, P.F. and McCloskey, J.A.

Structure determination of a nucleoside Q precursor isolated from

E. coli

tRNA: 7-(aminomethyl)-

7-deazaguanosine.

Nucleic Acids Res.

5 (1978) 2289–2296. [PMID:

353740

]

5. Noguchi, S., Yamaizumi, Z., Ohgi, T., Goto, T., Nishimura, Y., Hirota, Y. and Nishimura, S.

Isolation of Q nucleoside precursor present in tRNA of an

E. coli

mutant and its characterization

as 7-(cyano)-7-deazaguanosine.

Nucleic Acids Res.

5 (1978) 4215–4223. [PMID:

364423

]

6. Swairjo, M.A., Reddy, R.R., Lee, B., Van Lanen, S.G., Brown, S., de Crécy-Lagard, V., Iwata-

Reuyl, D. and Schimmel, P. Crystallization and preliminary X-ray characterization of the nitrile
reductase QueF: a queuosine-biosynthesis enzyme.

Acta Crystallogr. F Struct. Biol. Crystal. Co

61 (2005) 945–948.

[EC 1.7.1.13 created 2006]

*EC 1.8.1.4

Common name: dihydrolipoyl dehydrogenase

Reaction: protein 6-

-(dihydrolipoyl)lysine + NAD

= protein 6-

-(lipoyl)lysine + NADH + H

For diagram of oxo-acid dehydrogenase complexes,

click here

, for diagram of the citric-acid cycle,

click here

and for diagram of the glycine-cleavage system,

click here

Glossary:

dihydrolipoyl group

Other name(s): LDP-Glc; LDP-Val; dehydrolipoate dehydrogenase; diaphorase; dihydrolipoamide dehydrogenase;

dihydrolipoamide:NAD

oxidoreductase; dihydrolipoic dehydrogenase; dihydrothioctic

dehydrogenase; lipoamide dehydrogenase (NADH); lipoamide oxidoreductase (NADH); lipoamide
reductase; lipoamide reductase (NADH); lipoate dehydrogenase; lipoic acid dehydrogenase; lipoyl
dehydrogenase; protein-

-(dihydrolipoyl)lysine:NAD

oxidoreductase

Systematic name: protein-6-

-(dihydrolipoyl)lysine:NAD

oxidoreductase

Comments: A flavoprotein (FAD). A component of the multienzyme 2-oxo-acid dehydrogenase complexes. In

the pyruvate dehydrogenase complex, it binds to the core of

EC 2.3.1.12

, dihydrolipoyllysine-

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residue acetyltransferase, and catalyses oxidation of its dihydrolipoyl groups. It plays a similar role
in the oxoglutarate and 3-methyl-2-oxobutanoate dehydrogenase complexes. Another substrate is
the dihydrolipoyl group in the H-protein of the glycine-cleavage system (

click here

for diagram), in

which it acts, together with

EC 1.4.4.2

, glycine dehydrogenase (decarboxylating), and

EC 2.1.2.10

aminomethyltransferase, to break down glycine. It can also use free dihydrolipoate,
dihydrolipoamide or dihydrolipoyllysine as substrate. This enzyme was first shown to catalyse the
oxidation of NADH by methylene blue; this activity was called diaphorase. The glycine cleavage
system is composed of four components that only loosely associate: the P protein (

EC 1.4.4.2

), the

T protein (

EC 2.1.2.10

), the L protein (EC 1.8.1.4) and the lipoyl-bearing H protein [6].

Links to other databases:

BRENDA

EXPASY

IUBMB

KEGG

PDB

, CAS registry number: 9001-18-7

References: 1. Massey, V. Lipoyl dehydrogenase. In: Boyer, P.D., Lardy, H. and MyrbÃ¤ck, K. (Eds),

The

Enzymes

, 2nd edn, vol. 7, Academic Press, New York, 1963, pp. 275–306.

2. Massey, V., Gibson, Q.H. and Veeger, C. Intermediates in the catalytic action of lipoyl

dehydrogenase (diaphorase).

Biochem. J.

77 (1960) 341–351. [PMID:

13767908

]

3. Savage, N. Preparation and properties of highly purified diaphorase.

Biochem. J.

67 (1957) 146–

155. [PMID:

13471525

]

4. Straub, F.B. Isolation and properties of a flavoprotein from heart muscle tissue.

Biochem. J.

(1939) 787–792.

5. Perham, R.N. Swinging arms and swinging domains in multifunctional enzymes: catalytic

machines for multistep reactions.

Annu. Rev. Biochem.

69 (2000) 961–1004. [PMID:

10966480

]

6. Nesbitt, N.M., Baleanu-Gogonea, C., Cicchillo, R.M., Goodson, K., Iwig, D.F., Broadwater, J.A.,

Haas, J.A., Fox, B.G. and Booker, S.J. Expression, purification, and physical characterization of

Escherichia coli

lipoyl(octanoyl)transferase.

Protein Expr. Purif.

39 (2005) 269–282. [PMID:

15642479

]

[EC 1.8.1.4 created 1961 as EC 1.6.4.3, modified 1976, transferred 1983 to EC 1.8.1.4, modified 2003, modified 2006]

*EC 1.11.1.14

Common name: lignin peroxidase

Reaction: 1,2-bis(3,4-dimethoxyphenyl)propane-1,3-diol + H

= 3,4-dimethoxybenzaldehyde + 1-(3,4-

dimethoxyphenyl)ethane-1,2-diol + H

For diagram of reaction,

click here

Other name(s): diarylpropane oxygenase; ligninase I; diarylpropane peroxidase; LiP;

diarylpropane:oxygen,hydrogen-peroxide oxidoreductase (C-C-bond-cleaving)

Systematic name: 1,2-bis(3,4-dimethoxyphenyl)propane-1,3-diol:hydrogen-peroxide oxidoreductase

Comments: A hemoprotein. Brings about the oxidative cleavage of C-C and ether (C-O-C) bonds in a number

of lignin model compounds (of the diarylpropane and arylpropane-aryl ether type). The enzyme
also oxidizes benzyl alcohols to aldehydes, via an aromatic cation radical [9]. Involved in the
oxidative breakdown of lignin in white rot basidiomycetes. Molecular oxygen may be involved in the
reaction of substrate radicals under aerobic conditions [3,8].

Links to other databases:

BRENDA

ERGO

EXPASY

IUBMB

KEGG

PDB

, CAS registry number: 93792-13-3

References: 1. Paszczynski, A., Huynh, V.-B. and Crawford, R. Comparison of ligninase-I and peroxidase-M2

from the white-rot fungus

Phanerochaete chrysosporium

Arch. Biochem. Biophys.

244 (1986)

750–765. [PMID:

3080953

]

2. Renganathan, V., Miki, K. and Gold, M.H. Multiple molecular forms of diarylpropane oxygenase,

an H

-requiring, lignin-degrading enzyme from

Phanerochaete chrysosporium

Arch.

Biochem. Biophys.

241 (1985) 304–314. [PMID:

4026322

]

3. Tien, M. and Kirk, T.T. Lignin-degrading enzyme from

Phanerochaete chrysosporium

;

purification, characterization, and catalytic properties of a unique H

-requiring oxygenase.

Proc. Natl. Acad. Sci. USA

81 (1984) 2280–2284.

4. Doyle, W.A., Blodig, W., Veitch, N.C., Piontek, K. and Smith, A.T. Two substrate interaction

sites in lignin peroxidase revealed by site-directed mutagenesis.

Biochemistry

37 (1998) 15097–

15105. [PMID:

9790672

]

5. Wariishi, H., Marquez, L., Dunford, H.B. and Gold, M.H. Lignin peroxidase compounds II and

III. Spectral and kinetic characterization of reactions with peroxides.

J. Biol. Chem.

265 (1990)

11137–11142. [PMID:

2162833

]

6. Cai, D.Y. and Tien, M. Characterization of the oxycomplex of lignin peroxidases from

Phanerochaete chrysosporium

: equilibrium and kinetics studies.

Biochemistry

29 (1990) 2085–

2091. [PMID:

2328240

]

7. Tien, M. and Tu, C.P. Cloning and sequencing of a cDNA for a ligninase from

Phanerochaete

chrysosporium

Nature

326 (1987) 520–523. [PMID:

3561490

]

8. Renganathan, V., Miki, K. and Gold, M.H. Role of molecular oxygen in lignin peroxidase

reactions.

Arch. Biochem. Biophys.

246 (1986) 155–161. [PMID:

3754412

]

06/27/2006 05:11 PM

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http://www.enzyme-database.org/newenz.php?sp=off

9. Kersten, P.J., Tien, M., Kalyanaraman, B. and Kirk, T.K. The ligninase of

Phanerochaete

chrysosporium

generates cation radicals from methoxybenzenes.

J. Biol. Chem.

260 (1985)

2609–2612. [PMID:

2982828

]

10. Kirk, T.K. and Farrell, R.L. Enzymatic "combustion": the microbial degradation of lignin.

Annu.

Rev. Microbiol.

41 (1987) 465–505. [PMID:

3318677

]

[EC 1.11.1.14 created 1992, modified 2006]

EC 1.11.1.16

Common name: versatile peroxidase

Reaction: (1) Reactive Black 5 + H

= oxidized Reactive Black 5 + 2 H

(2) donor + H

= oxidized donor + 2 H

Glossary: reactive black 5 = tetrasodium 4-amino-5-hydroxy-3,6(bis(4-(2-

(sulfonatooxy)ethylsulfonyl)phenyl)azo)-naphthalene-2,7-disulfonate

Other name(s): VP; hybrid peroxidase; polyvalent peroxidase

Systematic name: reactive-black-5:hydrogen-peroxide oxidoreductase

Comments: A hemoprotein. This ligninolytic peroxidase combines the substrate-specificity characteristics of the

two other ligninolytic peroxidases,

EC 1.11.1.13

, manganese peroxidase and

EC 1.11.1.14

, lignin

peroxidase. It is also able to oxidize phenols, hydroquinones and both low- and high-redox-
potential dyes, due to a hybrid molecular architecture that involves multiple binding sites for
substrates [2,4].

References: 1. Martínez, M.J., Ruiz-Dueñas, F.J., Guillén, F. and Martínez, A.T. Purification and catalytic

properties of two manganese peroxidase isoenzymes from

Pleurotus eryngii

Eur. J. Biochem.

237 (1996) 424–432. [PMID:

8647081

]

2. Heinfling, A., Ruiz-Dueñas, F.J., Martínez, M.J., Bergbauer, M., Szewzyk, U. and Martínez, A.T.

A study on reducing substrates of manganese-oxidizing peroxidases from

Pleurotus eryngii

and

Bjerkandera adusta

FEBS Lett.

428 (1998) 141–146. [PMID:

9654123

]

3. Ruiz-Dueñas, F.J., Martínez, M.J. and Martínez, A.T. Molecular characterization of a novel

peroxidase isolated from the ligninolytic fungus

Pleurotus eryngii

Mol. Microbiol.

31 (1999) 223–

235. [PMID:

9987124

]

4. Camarero, S., Sarkar, S., Ruiz-Dueñas, F.J., Martínez, M.J. and Martínez, A.T. Description of a

versatile peroxidase involved in the natural degradation of lignin that has both manganese
peroxidase and lignin peroxidase substrate interaction sites.

J. Biol. Chem.

274 (1999) 10324–

10330. [PMID:

10187820

]

5. Ruiz-Dueñas, F.J., Martínez, M.J. and Martínez, A.T. Heterologous expression of

Pleurotus

eryngii

peroxidase confirms its ability to oxidize Mn

and different aromatic substrates.

Appl.

Environ. Microbiol.

65 (1999) 4705–4707. [PMID:

10508113

]

6. Camarero, S., Ruiz-Dueñas, F.J., Sarkar, S., Martínez, M.J. and Martínez, A.T. The cloning of a

new peroxidase found in lignocellulose cultures of

Pleurotus eryngii

and sequence comparison

with other fungal peroxidases.

FEMS Microbiol. Lett.

191 (2000) 37–43. [PMID:

11004397

]

7. Ruiz-Dueñas, F.J., Camarero, S., Pérez-Boada, M., Martínez, M.J. and Martínez, A.T. A new

versatile peroxidase from

Pleurotus

Biochem. Soc. Trans.

29 (2001) 116–122. [PMID:

11356138

]

8. Banci, L., Camarero, S., Martínez, A.T., Martínez, M.J., Pérez-Boada, M., Pierattelli, R. and

Ruiz-Dueñas, F.J. NMR study of manganese(II) binding by a new versatile peroxidase from the
white-rot fungus

Pleurotus eryngii

J. Biol. Inorg. Chem.

8 (2003) 751–760. [PMID:

12884090

]

9. Pérez-Boada, M., Ruiz-Dueñas, F.J., Pogni, R., Basosi, R., Choinowski, T., Martínez, M.J.,

Piontek, K. and Martínez, A.T. Versatile peroxidase oxidation of high redox potential aromatic
compounds: site-directed mutagenesis, spectroscopic and crystallographic investigation of three
long-range electron transfer pathways.

J. Mol. Biol.

354 (2005) 385–402. [PMID:

16246366

]

10. Caramelo, L., Martínez, M.J. and Martínez, A.T. A search for ligninolytic peroxidases in the

fungus

Pleurotus eryngii

involving α-keto-γ-thiomethylbutyric acid and lignin model dimer.

Appl.

Environ. Microbiol.

65 (1999) 916–922. [PMID:

10049842

]

[EC 1.11.1.16 created 2006]

*EC 1.13.11.11

Common name: tryptophan 2,3-dioxygenase

Reaction:

-tryptophan + O

-formyl-

-kynurenine

For diagram of tryptophan catabolism,

click here

Other name(s): tryptophan pyrrolase (ambiguous); tryptophanase; tryptophan oxygenase; tryptamine 2,3-

06/27/2006 05:11 PM

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dioxygenase; tryptophan peroxidase; indoleamine 2,3-dioxygenase (ambiguous); indolamine 2,3-
dioxygenase (ambiguous);

-tryptophan pyrrolase; TDO;

-tryptophan 2,3-dioxygenase

Systematic name:

-tryptophan:oxygen 2,3-oxidoreductase (decyclizing)

Comments: A protohemoprotein. In mammals, the enzyme appears to be located only in the liver. This enzyme,

together with

EC 1.13.11.52

, indoleamine 2,3-dioxygenase, catalyses the first and rate-limiting step

in the kynurenine pathway, the major pathway of tryptophan metabolism [5]. The enzyme is specific
for tryptophan as substrate, but is far more active with

-tryptophan than with

-tryptophan [2].

Links to other databases:

BRENDA

ERGO

EXPASY

IUBMB

KEGG

, CAS registry number: 9014-51-1

References: 1. Uchida, K., Shimizu, T., Makino, R., Sakaguchi, K., Iizuka, T., Ishimura, Y., Nozawa, T. and

Hatano, M. Magnetic and natural circular dichroism of

-tryptophan 2,3-dioxygenases and

indoleamine 2,3-dioxygenase. I. Spectra of ferric and ferrous high spin forms.

J. Biol. Chem.

258

(1983) 2519–2525. [PMID:

6600455

]

2. Ren, S., Liu, H., Licad, E. and Correia, M.A. Expression of rat liver tryptophan 2,3-dioxygenase

Escherichia coli

: structural and functional characterization of the purified enzyme.

Arch.

Biochem. Biophys.

333 (1996) 96–102. [PMID:

8806758

]

3. Leeds, J.M., Brown, P.J., McGeehan, G.M., Brown, F.K. and Wiseman, J.S. Isotope effects and

alternative substrate reactivities for tryptophan 2,3-dioxygenase.

J. Biol. Chem.

268 (1993)

17781–17786. [PMID:

8349662

]

4. Dang, Y., Dale, W.E. and Brown, O.R. Comparative effects of oxygen on indoleamine 2,3-

dioxygenase and tryptophan 2,3-dioxygenase of the kynurenine pathway.

Free Radic. Biol. Med.

28 (2000) 615–624. [PMID:

10719243

]

5. Littlejohn, T.K., Takikawa, O., Truscott, R.J. and Walker, M.J. Asp

274

and His

346

are essential for

heme binding and catalytic function of human indoleamine 2,3-dioxygenase.

J. Biol. Chem.

278

(2003) 29525–29531. [PMID:

12766158

]

[EC 1.13.11.11 created 1961 as EC 1.11.1.4, deleted 1964, reinstated 1965 as EC 1.13.1.12, transferred 1972 to EC 1.13.11.11, modified 1989, modified

2006]

*EC 1.13.11.19

Common name: cysteamine dioxygenase

Reaction: 2-aminoethanethiol + O

= hypotaurine

For diagram of taurine biosynthesis,

click here

Other name(s): persulfurase; cysteamine oxygenase; cysteamine:oxygen oxidoreductase

Systematic name: 2-aminoethanethiol:oxygen oxidoreductase

Comments: A non-heme iron protein that is involved in the biosynthesis of taurine. Requires catalytic amounts

of a cofactor-like compound, such as sulfur, sufide, selenium or methylene blue for maximal
activity. 3-Aminopropanethiol (homocysteamine) and 2-mercaptoethanol can also act as substrates,
but glutathione, cysteine, and cysteine ethyl- and methyl esters are not good substrates [1,3].

Links to other databases:

BRENDA

ERGO

EXPASY

IUBMB

KEGG

, CAS registry number: 9033-41-4

References: 1. Cavallini, D., de Marco, C., Scandurra, R., Duprè, S. and Graziani, M.T. The enzymatic oxidation

of cysteamine to hypotaurine. Purification and properties of the enzyme.

J. Biol. Chem.

241

(1966) 3189–3196. [PMID:

5912113

]

2. Wood, J.L. and Cavallini, D. Enzymic oxidation of cysteamine to hypotaurine in the absence of a

cofactor.

Arch. Biochem. Biophys.

119 (1967) 368–372. [PMID:

6052430

]

3. Cavallini, D., Federici, G., Ricci, G., Duprè, S. and Antonucci, A. The specificity of cysteamine

oxygenase.

FEBS Lett.

56 (1975) 348–351. [PMID:

1157952

]

4. Richerson, R.B. and Ziegler, D.M. Cysteamine dioxygenase.

Methods Enzymol.

143 (1987) 410–

415. [PMID:

3657558

]

[EC 1.13.11.19 created 1972, modified 2006]

EC 1.13.11.42

Deleted entry: indoleamine-pyrrole 2,3-dioxygenase

[EC 1.13.11.42 created 1992, deleted 2006]

EC 1.13.11.52

Common name: indoleamine 2,3-dioxygenase

Reaction: (1)

-tryptophan + O

-formyl-

-kynurenine

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(2)

-tryptophan + O

-formyl-

-kynurenine

For diagram of tryptophan catabolism,

click here

Other name(s): IDO (ambiguous); tryptophan pyrrolase (ambiguous)

Systematic name:

-tryptophan:oxygen 2,3-oxidoreductase (decyclizing)

Comments: A protohemoprotein. Requires ascorbic acid and methylene blue for activity. This enzyme has

broader substrate specificity than

EC 1.13.11.11

, tryptophan 2,3-dioxygenase [1]. It is induced in

response to pathological conditions and host-defense mechanisms and its distribution in mammals
is not confined to the liver [2]. While the enzyme is more active with

-tryptophan than

tryptophan, its only known function to date is in the metabolism of

-tryptophan [2,6]. Superoxide

radicals can replace O

as oxygen donor [4,7].

References: 1. Yamamoto, S. and Hayaishi, O. Tryptophan pyrrolase of rabbit intestine.

- and

-tryptophan-

cleaving enzyme or enzymes.

J. Biol. Chem.

242 (1967) 5260–5266. [PMID:

6065097

]

2. Yasui, H., Takai, K., Yoshida, R. and Hayaishi, O. Interferon enhances tryptophan metabolism by

inducing pulmonary indoleamine 2,3-dioxygenase: its possible occurrence in cancer patients.

Proc. Natl. Acad. Sci. USA

83 (1986) 6622–6626. [PMID:

2428037

]

3. Takikawa, O., Yoshida, R., Kido, R. and Hayaishi, O. Tryptophan degradation in mice initiated by

indoleamine 2,3-dioxygenase.

J. Biol. Chem.

261 (1986) 3648–3653. [PMID:

2419335

]

4. Hirata, F., Ohnishi, T. and Hayaishi, O. Indoleamine 2,3-dioxygenase. Characterization and

properties of enzyme. O

complex.

J. Biol. Chem.

252 (1977) 4637–4642. [PMID:

194886

]

5. Dang, Y., Dale, W.E. and Brown, O.R. Comparative effects of oxygen on indoleamine 2,3-

dioxygenase and tryptophan 2,3-dioxygenase of the kynurenine pathway.

Free Radic. Biol. Med.

28 (2000) 615–624. [PMID:

10719243

]

6. Littlejohn, T.K., Takikawa, O., Truscott, R.J. and Walker, M.J. Asp

274

and His

346

are essential for

heme binding and catalytic function of human indoleamine 2,3-dioxygenase.

J. Biol. Chem.

278

(2003) 29525–29531. [PMID:

12766158

]

7. Thomas, S.R. and Stocker, R. Redox reactions related to indoleamine 2,3-dioxygenase and

tryptophan metabolism along the kynurenine pathway.

Redox Rep.

4 (1999) 199–220. [PMID:

10731095

]

8. Sono, M. Spectroscopic and equilibrium studies of ligand and organic substrate binding to

indolamine 2,3-dioxygenase.

Biochemistry

29 (1990) 1451–1460. [PMID:

2334706

]

[EC 1.13.11.52 created 2006]

EC 1.13.11.53

Common name: acireductone dioxygenase (Ni

-requiring)

Reaction: 1,2-dihydroxy-5-(methylthio)pent-1-en-3-one + O

= 3-(methylthio)propanoate + formate + CO

For diagram of methione-salvage pathway,

click here

and for mechanism of reaction,

click here

Glossary: acireductone = 1,2-dihydroxy-5-(methylthio)-pent-1-en-3-one

Other name(s): ARD; 2-hydroxy-3-keto-5-thiomethylpent-1-ene dioxygenase (ambiguous); acireductone

dioxygenase (ambiguous); E-2

Systematic name: 1,2-dihydroxy-5-(methylthio)pent-1-en-3-one:oxygen oxidoreductase (formate- and CO-forming)

Comments: Requires Ni

. If iron(II) is bound instead of Ni

, the reaction catalysed by

EC 1.13.11.54

acireductone dioxygenase [iron(II)-requiring], occurs instead [1]. The enzyme from the bacterium

Klebsiella oxytoca

(formerly

Klebsiella pneumoniae

) ATCC strain 8724 is involved in the methionine

salvage pathway.

References: 1. Wray, J.W. and Abeles, R.H. A bacterial enzyme that catalyzes formation of carbon monoxide.

Biol. Chem.

268 (1993) 21466–21469. [PMID:

8407993

]

2. Wray, J.W. and Abeles, R.H. The methionine salvage pathway in

Klebsiella pneumoniae

and rat

liver. Identification and characterization of two novel dioxygenases.

J. Biol. Chem.

270 (1995)

3147–3153. [PMID:

7852397

]

3. Furfine, E.S. and Abeles, R.H. Intermediates in the conversion of 5′-

-methylthioadenosine to

methionine in

Klebsiella pneumoniae

J. Biol. Chem.

263 (1988) 9598–9606. [PMID:

2838472

]

4. Dai, Y., Wensink, P.C. and Abeles, R.H. One protein, two enzymes.

J. Biol. Chem.

274 (1999)

1193–1195. [PMID:

9880484

]

5. Mo, H., Dai, Y., Pochapsky, S.S. and Pochapsky, T.C.

C and

N NMR assignments for a

carbon monoxide generating metalloenzyme from

Klebsiella pneumoniae

J. Biomol. NMR

(1999) 287–288. [PMID:

10481280

]

6. Dai, Y., Pochapsky, T.C. and Abeles, R.H. Mechanistic studies of two dioxygenases in the

methionine salvage pathway of

Klebsiella pneumoniae

Biochemistry

40 (2001) 6379–6387.

[PMID:

11371200

]

7. Al-Mjeni, F., Ju, T., Pochapsky, T.C. and Maroney, M.J. XAS investigation of the structure and

function of Ni in acireductone dioxygenase.

Biochemistry

41 (2002) 6761–6769. [PMID:

06/27/2006 05:11 PM

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12022880

]

8. Pochapsky, T.C., Pochapsky, S.S., Ju, T., Mo, H., Al-Mjeni, F. and Maroney, M.J. Modeling and

experiment yields the structure of acireductone dioxygenase from

Klebsiella pneumoniae

Nat.

Struct. Biol.

9 (2002) 966–972. [PMID:

12402029

]

[EC 1.13.11.53 created 2006]

EC 1.13.11.54

Common name: acireductone dioxygenase [iron(II)-requiring]

Reaction: 1,2-dihydroxy-5-(methylthio)pent-1-en-3-one + O

= 4-(methylthio)-2-oxobutanoate + formate

For diagram of methione-salvage pathway,

click here

and for mechanism of reaction,

click here

Other name(s): ARD′; 2-hydroxy-3-keto-5-thiomethylpent-1-ene dioxygenase (ambiguous); acireductone

dioxygenase (ambiguous); E-2′; E-3 dioxygenase

Systematic name: 1,2-dihydroxy-5-(methylthio)pent-1-en-3-one:oxygen oxidoreductase (formate-forming)

Comments: Requires iron(II). If Ni

is bound instead of iron(II), the reaction catalysed by

EC 1.13.11.53

acireductone dioxygenase (Ni

-requiring), occurs instead. The enzyme from the bacterium

Klebsiella oxytoca

(formerly

Klebsiella pneumoniae

) ATCC strain 8724 is involved in the methionine

salvage pathway.

References: 1. Wray, J.W. and Abeles, R.H. A bacterial enzyme that catalyzes formation of carbon monoxide.

Biol. Chem.

268 (1993) 21466–21469. [PMID:

8407993

]

2. Wray, J.W. and Abeles, R.H. The methionine salvage pathway in

Klebsiella pneumoniae

and rat

liver. Identification and characterization of two novel dioxygenases.

J. Biol. Chem.

270 (1995)

3147–3153. [PMID:

7852397

]

3. Furfine, E.S. and Abeles, R.H. Intermediates in the conversion of 5′-

-methylthioadenosine to

methionine in

Klebsiella pneumoniae

J. Biol. Chem.

263 (1988) 9598–9606. [PMID:

2838472

]

4. Dai, Y., Wensink, P.C. and Abeles, R.H. One protein, two enzymes.

J. Biol. Chem.

274 (1999)

1193–1195. [PMID:

9880484

]

5. Mo, H., Dai, Y., Pochapsky, S.S. and Pochapsky, T.C.

C and

N NMR assignments for a

carbon monoxide generating metalloenzyme from

Klebsiella pneumoniae

J. Biomol. NMR

(1999) 287–288. [PMID:

10481280

]

6. Dai, Y., Pochapsky, T.C. and Abeles, R.H. Mechanistic studies of two dioxygenases in the

methionine salvage pathway of

Klebsiella pneumoniae

Biochemistry

40 (2001) 6379–6387.

[PMID:

11371200

]

7. Al-Mjeni, F., Ju, T., Pochapsky, T.C. and Maroney, M.J. XAS investigation of the structure and

function of Ni in acireductone dioxygenase.

Biochemistry

41 (2002) 6761–6769. [PMID:

12022880

]

8. Pochapsky, T.C., Pochapsky, S.S., Ju, T., Mo, H., Al-Mjeni, F. and Maroney, M.J. Modeling and

experiment yields the structure of acireductone dioxygenase from

Klebsiella pneumoniae

Nat.

Struct. Biol.

9 (2002) 966–972. [PMID:

12402029

]

[EC 1.13.11.54 created 2006]

EC 1.13.11.55

Common name: sulfur oxygenase/reductase

Reaction: 4 sulfur + 4 H

O + O

= 2 hydrogen sulfide + 2 bisulfite + 2 H

Other name(s): SOR; sulfur oxygenase; sulfur oxygenase reductase

Systematic name: sulfur:oxygen oxidoreductase (hydrogen-sulfide- and sulfite-forming)

Comments: This enzyme, which is found in thermophilic microorganisms, contains one mononuclear none-

heme iron centre per subunit. Elemental sulfur is both the electron donor and one of the two known
acceptors, the other being oxygen. Another reaction product is thiosulfate, but this is probably
formed non-enzymically at elevated temperature from sulfite and sulfur [1]. This enzyme differs
from

EC 1.13.11.18

, sulfur dioxygenase and

EC 1.97.1.3

, sulfur reductase, in that both activities

are found together.

References: 1. Kletzin, A. Coupled enzymatic production of sulfite, thiosulfate, and hydrogen sulfide from sulfur:

purification and properties of a sulfur oxygenase reductase from the facultatively anaerobic
archaebacterium

Desulfurolobus ambivalens

J. Bacteriol.

171 (1989) 1638–1643. [PMID:

2493451

]

2. Kletzin, A. Molecular characterization of the sor gene, which encodes the sulfur

oxygenase/reductase of the thermoacidophilic Archaeum

Desulfurolobus ambivalens

Bacteriol.

174 (1992) 5854–5859. [PMID:

1522063

]

3. Sun, C.W., Chen, Z.W., He, Z.G., Zhou, P.J. and Liu, S.J. Purification and properties of the sulfur

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oxygenase/reductase from the acidothermophilic archaeon,

Acidianus

strain S5.

Extremophiles

(2003) 131–134. [PMID:

12664265

]

4. Urich, T., Bandeiras, T.M., Leal, S.S., Rachel, R., Albrecht, T., Zimmermann, P., Scholz, C.,

Teixeira, M., Gomes, C.M. and Kletzin, A. The sulphur oxygenase reductase from

Acidianus

ambivalens

is a multimeric protein containing a low-potential mononuclear non-haem iron centre.

Biochem. J.

381 (2004) 137–146. [PMID:

15030315

]

[EC 1.13.11.55 created 2006]

EC 1.13.12.14

Common name: chlorophyllide-

oxygenase

Reaction: (1) chlorophyllide

+ O

+ NADPH + H

= 7-hydroxychlorophyllide

+ H

O + NADP

(2) 7-hydroxychlorophyllide

+ O

+ NADPH + H

= chlorophyllide

+ 2 H

O + NADP

Other name(s): chlorophyllide

oxygenase; cholorophyll-b synthase; CAO

Systematic name: chlorophyllide-

:oxygen 7-oxidoreductase

Comments: Chlorophyll

is required for the assembly of stable light-harvesting complexes (LHCs) in the

chloroplast of green algae, cyanobacteria and plants [2,3]. Contains a mononuclear iron centre [3].
The enzyme catalyses two successive hydroxylations at the 7-methyl group of chlorophyllide

. The

second step yields the aldehyde hydrate, which loses H

O spontaneously to form chlorophyllide

[2]. Chlorophyll

and protochlorophyllide

are not substrates [2].

References: 1. Espineda, C.E., Linford, A.S., Devine, D. and Brusslan, J.A. The

AtCAO

gene, encoding

chlorophyll

oxygenase, is required for chlorophyll

synthesis in

Arabidopsis thaliana

Proc.

Natl. Acad. Sci. USA

96 (1999) 10507–10511. [PMID:

10468639

]

2. Oster, U., Tanaka, R., Tanaka, A. and Rudiger, W. Cloning and functional expression of the

gene encoding the key enzyme for chlorophyll

biosynthesis (CAO) from

Arabidopsis thaliana

Plant J.

21 (2000) 305–310. [PMID:

10758481

]

3. Eggink, L.L., LoBrutto, R., Brune, D.C., Brusslan, J., Yamasato, A., Tanaka, A. and Hoober, J.K.

Synthesis of chlorophyll

: localization of chlorophyllide

oxygenase and discovery of a stable

radical in the catalytic subunit.

BMC Plant Biol.

4 (2004) 5 only. [PMID:

15086960

]

4. Porra, R.J., Schafer, W., Cmiel, E., Katheder, I. and Scheer, H. The derivation of the formyl-

group oxygen of chlorophyll

in higher plants from molecular oxygen. Achievement of high

enrichment of the 7-formyl-group oxygen from

in greening maize leaves.

Eur. J. Biochem.

219 (1994) 671–679. [PMID:

8307032

]

[EC 1.13.12.14 created 2006]

EC 1.14.13.65

Deleted entry: 2-hydroxyquinoline 8-monooxygenase

[EC 1.14.13.65 created 1999, deleted 2006]

EC 1.14.13.101

Common name: senecionine

-oxygenase

Reaction: senecionine + NADPH + H

+ O

= senecionine

-oxide + NADP

+ H

Other name(s): senecionine monooxygenase (

-oxide-forming); SNO

Systematic name: senecionine,NADPH:oxygen oxidoreductase (

-oxide-forming)

Comments: A flavoprotein. NADH cannot replace NADPH. While pyrrolizidine alkaloids of the senecionine and

monocrotaline types are generally good substrates (e.g. senecionine, retrorsine and monocrotaline),
the enzyme does not use ester alkaloids lacking an hydroxy group at C-7 (e.g. supinine and
phalaenopsine), 1,2-dihydro-alkaloids (e.g. sarracine) or unesterified necine bases (e.g. senkirkine)
as substrates [1]. Senecionine

-oxide is used by insects as a chemical defense: senecionine

oxide is non-toxic, but it is bioactivated to a toxic form by the action of cytochrome

-450 oxidase

when absorbed by insectivores.

Links to other databases: CAS registry number: 220581-68-0

References: 1. Lindigkeit, R., Biller, A., Buch, M., Schiebel, H.M., Boppre, M. and Hartmann, T. The two facies

of pyrrolizidine alkaloids: the role of the tertiary amine and its

-oxide in chemical defense of

insects with acquired plant alkaloids.

Eur. J. Biochem.

245 (1997) 626–636. [PMID:

9182998

]

2. Naumann, C., Hartmann, T. and Ober, D. Evolutionary recruitment of a flavin-dependent

monooxygenase for the detoxification of host plant-acquired pyrrolizidine alkaloids in the

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alkaloid-defended arctiid moth

Tyria jacobaeae

Proc. Natl. Acad. Sci. USA

99 (2002) 6085–

6090. [PMID:

11972041

]

[EC 1.14.13.101 created 2006]

*EC 1.14.99.3

Common name: heme oxygenase

Reaction: heme + 3 AH

+ 3 O

= biliverdin + Fe

+ CO + 3 A + 3 H

For diagram of the reaction mechanism,

click here

Other name(s): ORP33 proteins; haem oxygenase; heme oxygenase (decyclizing); heme oxidase; haem oxidase

Systematic name: heme,hydrogen-donor:oxygen oxidoreductase (α-methene-oxidizing, hydroxylating)

Comments: Requires NAD(P)H and

EC 1.6.2.4

, NADPH—hemoprotein reductase. The terminal oxygen atoms

that are incorporated into the carbonyl groups of pyrrole rings A and B of biliverdin are derived from
two separate oxygen molecules [4]. The third oxygen molecule provides the oxygen atom that
converts the α-carbon to CO. The central iron is kept in the reduced state by NAD(P)H.

Links to other databases:

BRENDA

ERGO

EXPASY

IUBMB

KEGG

PDB

, CAS registry number: 9059-22-7

References: 1. Maines, M.D., Ibrahim, N.G. and Kappas, K. Solubilization and partial purification of heme

oxygenase from rat liver.

J. Biol. Chem.

252 (1977) 5900–5903. [PMID:

18477

]

2. Sunderman, F.W., Jr., Downs, J.R., Reid, M.C. and Bibeau, L.M. Gas-chromatographic assay for

heme oxygenase activity.

Clin. Chem.

28 (1982) 2026–2032. [PMID:

6897023

]

3. Yoshida, T., Takahashi, S. and Kikuchi, J. Partial purification and reconstitution of the heme

oxygenase system from pig spleen microsomes.

J. Biochem. (Tokyo)

75 (1974) 1187–1191.

[PMID:

4370250

]

4. Noguchi, M., Yoshida, T. and Kikuchi, G. Specific requirement of NADPH-cytochrome

reductase for the microsomal heme oxygenase reaction yielding biliverdin IX α.

FEBS Lett.

(1979) 281–284. [PMID:

105935

]

5. Lad, L., Schuller, D.J., Shimizu, H., Friedman, J., Li, H., Ortiz de Montellano, P.R. and Poulos,

T.L. Comparison of the heme-free and -bound crystal structures of human heme oxygenase-1.

Biol. Chem.

278 (2003) 7834–7843. [PMID:

12500973

]

[EC 1.14.99.3 created 1972, modified 2006]

EC 1.17.99.4

Common name: uracil/thymine dehydrogenase

Reaction: (1) uracil + H

O + acceptor = barbiturate + reduced acceptor

(2) thymine + H

O + acceptor = 5-methylbarbiturate + reduced acceptor

For diagram of pyrimidine catabolism,

click here

Other name(s): uracil oxidase; uracil-thymine oxidase; uracil dehydrogenase

Systematic name: uracil:acceptor oxidoreductase

Comments: Forms part of the oxidative pyrimidine-degrading pathway in some microorganisms, along with

3.5.2.1

(barbiturase) and

EC 3.5.1.95

(

-malonylurea hydrolase). Mammals, plants and other

microorganisms utilize the reductive pathway, comprising

EC 1.3.1.1

[dihydrouracil dehydrogenase

(NAD

)] or

EC 1.3.1.2

[dihydropyrimidine dehydrogenase (NADP

)],

EC 3.5.2.2

(dihydropyrimidinase) and

EC 3.5.1.6

(β-ureidopropionase), with the ultimate degradation products

being an

-amino acid, NH

and CO

[5].

Links to other databases: CAS registry number: 9029-00-9

References: 1. Hayaishi, O. and Kornberg, A. Metabolism of cytosine, thymine, uracil, and barbituric acid by

bacterial enzymes.

J. Biol. Chem.

197 (1952) 717–723. [PMID:

12981104

]

2. Wang, T.P. and Lampen, J.O. Metabolism of pyrimidines by a soil bacterium.

J. Biol. Chem.

194

(1952) 775–783. [PMID:

14927671

]

3. Wang, T.P. and Lampen, J.O. Uracil oxidase and the isolation of barbituric acid from uracil

oxidation.

J. Biol. Chem.

194 (1952) 785–791. [PMID:

14927672

]

4. Lara, F.J.S. On the decomposition of pyrimidines by bacteria. II. Studies with cell-free enzyme

preparations.

J. Bacteriol.

64 (1952) 279–285. [PMID:

14955523

]

5. Soong, C.L., Ogawa, J. and Shimizu, S. Novel amidohydrolytic reactions in oxidative pyrimidine

metabolism: analysis of the barbiturase reaction and discovery of a novel enzyme,
ureidomalonase.

Biochem. Biophys. Res. Commun.

286 (2001) 222–226. [PMID:

11485332

]

[EC 1.17.99.4 created 1961 as EC 1.2.99.1, transferred 1984 to EC 1.1.99.19, transferred 2006 to EC 1.17.99.4]

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*EC 2.1.2.10

Common name: aminomethyltransferase

Reaction: [protein]-

-aminomethyldihydrolipoyllysine + tetrahydrofolate = [protein]-dihydrolipoyllysine + 5,10-

methylenetetrahydrofolate + NH

For diagram of the glycine-cleavage system,

click here

Glossary:

dihydrolipoyl group

Other name(s):

-aminomethyldihydrolipoylprotein:(6

)-tetrahydrofolate aminomethyltransferase (ammonia-

forming); T-protein; glycine synthase; tetrahydrofolate aminomethyltransferase

Systematic name: [protein]-

-aminomethyldihydrolipoyllysine:tetrahydrofolate aminomethyltransferase (ammonia-

forming)

Comments: A component, with

EC 1.4.4.2

glycine dehydrogenase (decarboxylating) and

EC 1.8.1.4

dihydrolipoyl dehydrogenanse, of the glycine cleavage system, formerly known as glycine synthase.
The glycine cleavage system is composed of four components that only loosely associate: the P
protein (

EC 1.4.4.2

), the T protein (EC 2.1.2.10), the L protein (

EC 1.8.1.4

) and the lipoyl-bearing H

protein [3].

Links to other databases:

BRENDA

ERGO

EXPASY

IUBMB

KEGG

, CAS registry number: 37257-08-2

References: 1. Okamura-Ikeda, J., Fujiwara, K. and Motokawa, Y. Purification and characterization of chicken

liver T protein, a component of the glycine cleavage system.

J. Biol. Chem.

257 (1982) 135–139.

[PMID:

7053363

]

2. Perham, R.N. Swinging arms and swinging domains in multifunctional enzymes: catalytic

machines for multistep reactions.

Annu. Rev. Biochem.

69 (2000) 961–1004. [PMID:

10966480

]

3. Nesbitt, N.M., Baleanu-Gogonea, C., Cicchillo, R.M., Goodson, K., Iwig, D.F., Broadwater, J.A.,

Haas, J.A., Fox, B.G. and Booker, S.J. Expression, purification, and physical characterization of

Escherichia coli

lipoyl(octanoyl)transferase.

Protein Expr. Purif.

39 (2005) 269–282. [PMID:

15642479

]

[EC 2.1.2.10 created 1972, modified 2003, modified 2006]

*EC 2.3.1.11

Common name: thioethanolamine

-acetyltransferase

Reaction: acetyl-CoA + 2-aminoethanethiol = CoA +

-(2-aminoethyl)thioacetate

Other name(s): thioltransacetylase B; thioethanolamine acetyltransferase; acetyl-CoA:thioethanolamine

acetyltransferase

Systematic name: acetyl-CoA:2-aminoethanethiol

-acetyltransferase

Comments: 2-Sulfanylethanol (2-mercaptoethanol) can act as a substrate [1].

Links to other databases:

BRENDA

ERGO

EXPASY

IUBMB

KEGG

, CAS registry number: 9029-93-0

References: 1. Brady, R.O. and Stadtman, E.R. Enzymatic thioltransacetylation.

J. Biol. Chem.

211 (1954) 621–

629. [PMID:

13221570

]

2. Gunsalus, I.C. Group transfer and acyl-generating functions of lipoic acid derivatives. In:

McElroy, W.D. and Glass, B. (Eds),

A Symposium on the Mechanism of Enzyme Action

, Johns

Hopkins Press, Baltimore, 1954, pp. 545–580.

[EC 2.3.1.11 created 1961, modified 2006]

*EC 2.3.1.38

Common name: [acyl-carrier-protein]

-acetyltransferase

Reaction: acetyl-CoA + [acyl-carrier-protein] = CoA + acetyl-[acyl-carrier-protein]

Other name(s): acetyl coenzyme A-acyl-carrier-protein transacylase; [acyl-carrier-protein]acetyltransferase;

[ACP]acetyltransferase; ACAT

Systematic name: acetyl-CoA:[acyl-carrier-protein]

-acetyltransferase

Comments: This enzyme, along with

EC 2.3.1.39

, [acyl-carrier-protein]

-malonyltransferase, is essential for

the initiation of fatty-acid biosynthesis in bacteria. The substrate acetyl-CoA protects the enzyme
against inhibition by

-ethylmaleimide or iodoacetamide [4]. This is one of the activities associated

with β-ketoacyl-ACP synthase III (

EC 2.3.1.180

) [5].

Links to other databases:

BRENDA

ERGO

EXPASY

GTD

IUBMB

KEGG

, CAS registry number: 37257-16-2

References: 1. Prescott, D.J. and Vagelos, P.R. Acyl carrier protein.

Adv. Enzymol. Relat. Areas Mol. Biol.

(1972) 269–311. [PMID:

4561013

]

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2. Vance, D.E., Mituhashi, O. and Bloch, K. Purification and properties of the fatty acid synthetase

from

Mycobacterium phlei

J. Biol. Chem.

248 (1973) 2303–2309. [PMID:

4698221

]

3. Williamson, I.P. and Wakil, S.J. Studies on the mechanism of fatty acid synthesis. XVII.

Preparation and general properties of acetyl coenzyme A and malonyl coenzyme A-acyl carrier
protein transacylases.

J. Biol. Chem.

241 (1966) 2326–2332. [PMID:

5330116

]

4. Lowe, P.N. and Rhodes, S. Purification and characterization of [acyl-carrier-protein]

acetyltransferase from

Escherichia coli

Biochem. J.

250 (1988) 789–796. [PMID:

3291856

]

5. Tsay, J.T., Oh, W., Larson, T.J., Jackowski, S. and Rock, C.O. Isolation and characterization of

the β-ketoacyl-acyl carrier protein synthase III gene (

fabH

) from

Escherichia coli

K-12.

J. Biol.

Chem.

267 (1992) 6807–6814. [PMID:

1551888

]

6. Rangan, V.S. and Smith, S. Alteration of the substrate specificity of the malonyl-CoA/acetyl-

CoA:acyl carrier protein

-acyltransferase domain of the multifunctional fatty acid synthase by

mutation of a single arginine residue.

J. Biol. Chem.

272 (1997) 11975–11978. [PMID:

9115261

]

[EC 2.3.1.38 created 1972, modified 2006]

*EC 2.3.1.39

Common name: [acyl-carrier-protein]

-malonyltransferase

Reaction: malonyl-CoA + [acyl-carrier-protein] = CoA + malonyl-[acyl-carrier-protein]

Other name(s): malonyl coenzyme A-acyl carrier protein transacylase; malonyl transacylase; malonyl transferase;

malonyl-CoA-acyl carrier protein transacylase; [acyl carrier protein]malonyltransferase; MAT; FabD;
malonyl-CoA:acyl carrier protein transacylase; malonyl-CoA:ACP transacylase; MCAT; malonyl-
CoA:AcpM transacylase

Systematic name: malonyl-CoA:[acyl-carrier-protein]

-malonyltransferase

Comments: This enzyme, along with

EC 2.3.1.38

, [acyl-carrier-protein]

-acetyltransferase, is essential for the

initiation of fatty-acid biosynthesis in bacteria. This enzyme also provides the malonyl groups for
polyketide biosynthesis [7]. The product of the reaction, malonyl-ACP, is an elongation substrate in
fatty-acid biosynthesis. In

Mycobacterium tuberculosis

, holo-ACP (the product of

EC 2.7.8.7

, holo-

[acyl-carrier-protein] synthase) is the preferred substrate [5].

Links to other databases:

BRENDA

ERGO

EXPASY

GTD

IUBMB

KEGG

PDB

, CAS registry number: 37257-17-3

References: 1. Alberts, A.W., Majerus, P.W. and Vagelos, P.R. Acetyl-CoA acyl carrier protein transacylase.

Methods Enzymol.

14 (1969) 50–53.

2. Prescott, D.J. and Vagelos, P.R. Acyl carrier protein.

Adv. Enzymol. Relat. Areas Mol. Biol.

(1972) 269–311. [PMID:

4561013

]

3. Williamson, I.P. and Wakil, S.J. Studies on the mechanism of fatty acid synthesis. XVII.

Preparation and general properties of acetyl coenzyme A and malonyl coenzyme A-acyl carrier
protein transacylases.

J. Biol. Chem.

241 (1966) 2326–2332. [PMID:

5330116

]

4. Joshi, V.C. and Wakil, S.J. Studies on the mechanism of fatty acid synthesis. XXVI. Purification

and properties of malonyl-coenzyme A

-acyl carrier protein transacylase of

Escherichia coli

Arch. Biochem. Biophys.

143 (1971) 493–505. [PMID:

4934182

]

5. Kremer, L., Nampoothiri, K.M., Lesjean, S., Dover, L.G., Graham, S., Betts, J., Brennan, P.J.,

Minnikin, D.E., Locht, C. and Besra, G.S. Biochemical characterization of acyl carrier protein
(AcpM) and malonyl-CoA:AcpM transacylase (mtFabD), two major components of

Mycobacterium tuberculosis

fatty acid synthase II.

J. Biol. Chem.

276 (2001) 27967–27974.

[PMID:

11373295

]

6. Keatinge-Clay, A.T., Shelat, A.A., Savage, D.F., Tsai, S.C., Miercke, L.J., O'Connell, J.D., 3rd,

Khosla, C. and Stroud, R.M. Catalysis, specificity, and ACP docking site of

Streptomyces

coelicolor

malonyl-CoA:ACP transacylase.

Structure

11 (2003) 147–154. [PMID:

12575934

]

7. Szafranska, A.E., Hitchman, T.S., Cox, R.J., Crosby, J. and Simpson, T.J. Kinetic and

mechanistic analysis of the malonyl CoA:ACP transacylase from

Streptomyces coelicolor

indicates a single catalytically competent serine nucleophile at the active site.

Biochemistry

(2002) 1421–1427. [PMID:

11814333

]

[EC 2.3.1.39 created 1972, modified 2006]

*EC 2.3.1.41

Common name: β-ketoacyl-acyl-carrier-protein synthase I

Reaction: an acyl-[acyl-carrier-protein] + malonyl-[acyl-carrier-protein] = a 3-oxoacyl-[acyl-carrier-protein] +

+ [acyl-carrier-protein]

Glossary: an acyl-[acyl-carrier-protein] =

-CO-[acyl-carrier-protein]

malonyl-[acyl-carrier-protein] = HOOC-CH

-CO-[acyl-carrier-protein]

a 3-oxoacyl-[acyl-carrier-protein] =

-CO-CH

-CO-[acyl-carrier-protein]

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Other name(s): β-ketoacyl-ACP synthase I; β-ketoacyl synthetase; β-ketoacyl-ACP synthetase; β-ketoacyl-acyl

carrier protein synthetase; β-ketoacyl-[acyl carrier protein] synthase; β-ketoacylsynthase;
condensing enzyme; 3-ketoacyl-acyl carrier protein synthase; fatty acid condensing enzyme; acyl-
malonyl(acyl-carrier-protein)-condensing enzyme; acyl-malonyl acyl carrier protein-condensing
enzyme; β-ketoacyl acyl carrier protein synthase; 3-oxoacyl-[acyl-carrier-protein] synthase; 3-
oxoacyl:ACP synthase I; KASI; KAS I; FabF1; FabB

Systematic name: acyl-[acyl-carrier-protein]:malonyl-[acyl-carrier-protein]

-acyltransferase (decarboxylating)

Comments: This enzyme is responsible for the chain-elongation step of dissociated (type II) fatty-acid

biosynthesis, i.e. the addition of two C atoms to the fatty-acid chain.

Escherichia coli

mutants that

lack this enzyme are deficient in unsaturated fatty acids. The enzyme can use fatty acyl thioesters
of ACP (C

to C

) as substrates, as well as fatty acyl thioesters of Co-A (C

to C

) [4]. The

substrate specificity is very similar to that of

EC 2.3.1.179

, β-ketoacyl-ACP synthase II, with the

exception that the latter enzyme is far more active with palmitoleoyl-ACP (C

) as substrate,

allowing the organism to regulate its fatty-acid composition with changes in temperature [4,5].

Links to other databases:

BRENDA

ERGO

EXPASY

IUBMB

KEGG

PDB

, CAS registry number: 9077-10-5

References: 1. Alberts, A.W., Majerus, P.W. and Vagelos, P.R. Acetyl-CoA acyl carrier protein transacylase.

Methods Enzymol.

14 (1969) 50–53.

2. Prescott, D.J. and Vagelos, P.R. Acyl carrier protein.

Adv. Enzymol. Relat. Areas Mol. Biol.

(1972) 269–311. [PMID:

4561013

]

3. Toomey, R.E. and Wakil, S.J. Studies on the mechanism of fatty acid synthesis. XVI. Preparation

and general properties of acyl-malonyl acyl carrier protein-condensing enzyme from

Escherichia

coli

J. Biol. Chem.

241 (1966) 1159–1165. [PMID:

5327099

]

4. D'Agnolo, G., Rosenfeld, I.S. and Vagelos, P.R. Multiple forms of β-ketoacyl-acyl carrier protein

synthetase in

Escherichia coli

J. Biol. Chem.

250 (1975) 5289–5294. [PMID:

237914

]

5. Garwin, J.L., Klages, A.L. and Cronan, J.E., Jr.. Structural, enzymatic, and genetic studies of β-

ketoacyl-acyl carrier protein synthases I and II of

Escherichia coli

J. Biol. Chem.

255 (1980)

11949–11956. [PMID:

7002930

]

6. Wang, H. and Cronan, J.E. Functional replacement of the FabA and FabB proteins of

Escherichia coli

fatty acid synthesis by

Enterococcus faecalis

FabZ and FabF homologues.

Biol. Chem.

279 (2004) 34489–34495. [PMID:

15194690

]

7. Cronan, J.E., Jr. and Rock, C.O. Biosynthesis of membrane lipids. In: Neidhardt, F.C. (Ed.),

Escherichia coli and Salmonella: Cellular and Molecular Biology

, 2nd edn, vol. 1, ASM Press,

Washington, DC, 1996, pp. 612–636.

[EC 2.3.1.41 created 1972, modified 2006]

*EC 2.3.1.109

Common name: arginine

-succinyltransferase

Reaction: succinyl-CoA +

-arginine = CoA + 2-

-succinyl-

-arginine

For diagram of arginine catabolism,

click here

Other name(s): arginine succinyltransferase; AstA; arginine and ornithine

-succinyltransferase; AOST; AST;

succinyl-CoA:

-arginine

-succinyltransferase

Systematic name: succinyl-CoA:

-arginine 2-

-succinyltransferase

Comments: Also acts on

-ornithine. This is the first enzyme in the arginine succinyltransferase (AST) pathway

for the catabolism of arginine [1]. This pathway converts the carbon skeleton of arginine into
glutamate, with the concomitant production of ammonia and conversion of succinyl-CoA into
succinate and CoA. The five enzymes involved in this pathway are EC 2.3.1.109 (arginine

succinyltransferase),

EC 3.5.3.23

(

-succinylarginine dihydrolase),

EC 2.6.1.81

(succinylornithine

transaminase),

EC 1.2.1.71

(succinylglutamate-semialdehyde dehydrogenase) and

EC 3.5.1.96

(succinylglutamate desuccinylase) [2,6].

Links to other databases:

BRENDA

ERGO

EXPASY

IUBMB

KEGG

, CAS registry number: 99676-48-9

References: 1. Vander Wauven, C., Jann, A., Haas, D., Leisinger, T. and Stalon, V.

-succinylornithine in

ornithine catabolism of

Pseudomonas aeruginosa

Arch. Microbiol.

150 (1988) 400–404. [PMID:

3144259

]

2. Vander Wauven, C. and Stalon, V. Occurrence of succinyl derivatives in the catabolism of

arginine in

Pseudomonas cepacia

J. Bacteriol.

164 (1985) 882–886. [PMID:

2865249

]

3. Tricot, C., Vander Wauven, C., Wattiez, R., Falmagne, P. and Stalon, V. Purification and

properties of a succinyltransferase from

Pseudomonas aeruginosa

specific for both arginine and

ornithine.

Eur. J. Biochem.

224 (1994) 853–861. [PMID:

7523119

]

4. Itoh, Y. Cloning and characterization of the

aru

genes encoding enzymes of the catabolic

arginine succinyltransferase pathway in

Pseudomonas aeruginosa

J. Bacteriol.

179 (1997)

7280–7290. [PMID:

9393691

]

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5. Schneider, B.L., Kiupakis, A.K. and Reitzer, L.J. Arginine catabolism and the arginine

succinyltransferase pathway in

Escherichia coli

J. Bacteriol.

180 (1998) 4278–4286. [PMID:

9696779

]

6. Cunin, R., Glansdorff, N., Pierard, A. and Stalon, V. Biosynthesis and metabolism of arginine in

bacteria.

Microbiol. Rev.

50 (1986) 314–352. [PMID:

3534538

]

7. Cunin, R., Glansdorff, N., Pierard, A. and Stalon, V. Erratum report: Biosynthesis and

metabolism of arginine in bacteria.

Microbiol. Rev.

51 (1987) 178 only.

[EC 2.3.1.109 created 1989, modified 2006]

EC 2.3.1.177

Common name: biphenyl synthase

Reaction: 3 malonyl-CoA + benzoyl-CoA = 4 CoA + 3,5-dihydroxybiphenyl + 4 CO

Other name(s): BIS

Systematic name: malonyl-CoA:benzoyl-CoA malonyltransferase

Comments: A polyketide synthase that is involved in the production of the phytoalexin aucuparin. 2-

Hydroxybenzoyl-CoA can also act as substrate but it leads to the derailment product 2-
hydroxybenzoyltriacetic acid lactone. This enzyme uses the same starter substrate as

2.3.1.151

, benzophenone synthase.

References: 1. Liu, B., Beuerle, T., Klundt, T. and Beerhues, L. Biphenyl synthase from yeast-extract-treated

cell cultures of

Sorbus aucuparia

Planta

218 (2004) 492–496. [PMID:

14595561

]

[EC 2.3.1.177 created 2006]

EC 2.3.1.178

Common name: diaminobutyrate acetyltransferase

Reaction: acetyl-CoA +

-2,4-diaminobutanoate = CoA + 4-

-acetyl-

-2,4-diaminobutanoate

For diagram of ectoine biosynthesis,

click here

Other name(s):

-2,4-diaminobutyrate acetyltransferase;

-2,4-diaminobutanoate acetyltransferase; EctA;

diaminobutyric acid acetyltransferase; DABA acetyltransferase; 2,4-diaminobutanoate
acetyltransferase; DAB acetyltransferase; DABAcT; acetyl-CoA:

-2,4-diaminobutanoate

acetyltransferase

Systematic name: acetyl-CoA:

-2,4-diaminobutanoate 4-

-acetyltransferase

Comments: Requires Na

or K

for maximal activity [3]. Ornithine, lysine, aspartate, and α-, β- and γ-

aminobutanoate cannot act as substrates [3]. However, acetyl-CoA can be replaced by propanoyl-
CoA, although the reaction proceeds more slowly [3]. Forms part of the ectoine-biosynthesis
pathway, the other enzymes involved being

EC 2.6.1.76

, diaminobutyrate—2-oxoglutarate

transaminase and

EC 4.2.1.108

, ectoine synthase.

References: 1. Peters, P., Galinski, E.A. and Truper, H.G. The biosynthesis of ectoine.

FEMS Microbiol. Lett.

(1990) 157–162.

2. Ono, H., Sawada, K., Khunajakr, N., Tao, T., Yamamoto, M., Hiramoto, M., Shinmyo, A., Takano,

M. and Murooka, Y. Characterization of biosynthetic enzymes for ectoine as a compatible solute
in a moderately halophilic eubacterium,

Halomonas elongata

J. Bacteriol.

181 (1999) 91–99.

[PMID:

9864317

]

3. Reshetnikov, A.S., Mustakhimov, I.I., Khmelenina, V.N. and Trotsenko, Y.A. Cloning, purification,

and characterization of diaminobutyrate acetyltransferase from the halotolerant methanotroph
Methylomicrobium alcaliphilum 20Z.

Biochemistry (Mosc.)

70 (2005) 878–883. [PMID:

16212543

]

4. Kuhlmann, A.U. and Bremer, E. Osmotically regulated synthesis of the compatible solute ectoine

Bacillus pasteurii

and related

Bacillus

spp.

Appl. Environ. Microbiol.

68 (2002) 772–783.

[PMID:

11823218

]

5. Louis, P. and Galinski, E.A. Characterization of genes for the biosynthesis of the compatible

solute ectoine from

Marinococcus halophilus

and osmoregulated expression in

Escherichia coli

Microbiology

143 (1997) 1141–1149. [PMID:

9141677

]

[EC 2.3.1.178 created 2006]

EC 2.3.1.179

Common name: β-ketoacyl-acyl-carrier-protein synthase II

Reaction: (

)-hexadec-11-enoyl-[acyl-carrier-protein] + malonyl-[acyl-carrier-protein] = (

)-3-oxooctadec-13-

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enoyl-[acyl-carrier-protein] + CO

+[acyl-carrier-protein]

For diagram of reaction,

click here

Glossary: (

)-hexadec-11-enoy-[acyl-carrier-protein] = palmitoleoyl-[acyl-carrier-protein]

(

)-3-oxooctadec-13-enoyl-[acyl-carrier-protein] = 3-oxovaccenoyl-[acyl-carrier-protein]

Other name(s): KASII; KAS II; FabF; 3-oxoacyl-acyl carrier protein synthase I; β-ketoacyl-ACP synthase II

Systematic name: (

)-hexadec-11-enoyl-[acyl-carrier-protein]:malonyl-[acyl-carrier-protein]

-acyltransferase

(decarboxylating)

Comments: Involved in the dissociated (or type II) fatty acid biosynthesis system that occurs in plants and

bacteria. While the substrate specificity of this enzyme is very similar to that of

EC 2.3.1.41

, β-

ketoacyl-ACP synthase I, it differs in that palmitoleoyl-ACP is not a good substrate of

EC 2.3.1.41

but is an excellent substrate of this enzyme [1,2]. The fatty-acid composition of

Escherichia coli

changes as a function of growth temperature, with the proportion of unsaturated fatty acids
increasing with lower growth temperature. This enzyme controls the temperature-dependent
regulation of fatty-acid composition, with mutants lacking this acivity being deficient in the
elongation of palmitoleate to

cis

-vaccenate at low temperatures [3,4].

References: 1. D'Agnolo, G., Rosenfeld, I.S. and Vagelos, P.R. Multiple forms of β-ketoacyl-acyl carrier protein

synthetase in

Escherichia coli

J. Biol. Chem.

250 (1975) 5289–5294. [PMID:

237914

]

2. Garwin, J.L., Klages, A.L. and Cronan, J.E., Jr.. Structural, enzymatic, and genetic studies of β-

ketoacyl-acyl carrier protein synthases I and II of

Escherichia coli

J. Biol. Chem.

255 (1980)

11949–11956. [PMID:

7002930

]

3. Price, A.C., Rock, C.O. and White, S.W. The 1.3-Angstrom-resolution crystal structure of β-

ketoacyl-acyl carrier protein synthase II from

Streptococcus pneumoniae

J. Bacteriol.

185

(2003) 4136–4143. [PMID:

12837788

]

4. Garwin, J.L., Klages, A.L. and Cronan, J.E., Jr. β-Ketoacyl-acyl carrier protein synthase II of

Escherichia coli

. Evidence for function in the thermal regulation of fatty acid synthesis.

J. Biol.

Chem.

255 (1980) 3263–3265. [PMID:

6988423

]

5. Magnuson, K., Carey, M.R. and Cronan, J.E., Jr. The putative

fabJ

gene of

Escherichia coli

fatty

acid synthesis is the

fabF

gene.

J. Bacteriol.

177 (1995) 3593–3595. [PMID:

7768872

]

6. Cronan, J.E., Jr. and Rock, C.O. Biosynthesis of membrane lipids. In: Neidhardt, F.C. (Ed.),

Escherichia coli and Salmonella: Cellular and Molecular Biology

, 2nd edn, vol. 1, ASM Press,

Washington, DC, 1996, pp. 612–636.

[EC 2.3.1.179 created 2006]

EC 2.3.1.180

Common name: β-ketoacyl-acyl-carrier-protein synthase III

Reaction: acetyl-CoA + malonyl-[acyl-carrier-protein] = acetoacetyl-[acyl-carrier-protein] + CoA + CO

Other name(s): 3-oxoacyl:ACP synthase III; 3-ketoacyl-acyl carrier protein synthase III; KASIII; KAS III; FabH; β-

ketoacyl-acyl carrier protein synthase III; β-ketoacyl-ACP synthase III; β-ketoacyl (acyl carrier
protein) synthase III

Systematic name: acetyl-CoA:malonyl-[acyl-carrier-protein]

-acyltransferase

Comments: Involved in the dissociated (or type II) fatty-acid biosynthesis system that occurs in plants and

bacteria. In contrast to

EC 2.3.1.41

(β-ketoacyl-ACP synthase I) and

EC 2.3.1.179

(β-ketoacyl-

ACP synthase II), this enzyme specifically uses CoA thioesters rather than acyl-ACP as the primer
[1]. In addition to the above reaction, the enzyme can also catalyse the reaction of

EC 2.3.1.38

[acyl-carrier-protein]

-acetyltransferase, but to a much lesser extent [1]. The enzyme is

responsible for initiating both straight- and branched-chain fatty-acid biosynthesis [2], with the
substrate specificity in an organism reflecting the fatty-acid composition found in that organism
[2,5]. For example,

Streptococcus pneumoniae

, a Gram-positive bacterium, is able to use both

straight- and branched-chain (C

—C

) acyl-CoA primers [3] whereas

Escherichia coli

, a Gram-

negative organism, uses primarily short straight-chain acyl CoAs, with a preference for acetyl-CoA
[4,5].

References: 1. Tsay, J.T., Oh, W., Larson, T.J., Jackowski, S. and Rock, C.O. Isolation and characterization of

the β-ketoacyl-acyl carrier protein synthase III gene (

fabH

) from

Escherichia coli

K-12.

J. Biol.

Chem.

267 (1992) 6807–6814. [PMID:

1551888

]

2. Han, L., Lobo, S. and Reynolds, K.A. Characterization of β-ketoacyl-acyl carrier protein

synthase III from

Streptomyces glaucescens

and its role in initiation of fatty acid biosynthesis.

Bacteriol.

180 (1998) 4481–4486. [PMID:

9721286

]

3. Khandekar, S.S., Gentry, D.R., Van Aller, G.S., Warren, P., Xiang, H., Silverman, C., Doyle,

M.L., Chambers, P.A., Konstantinidis, A.K., Brandt, M., Daines, R.A. and Lonsdale, J.T.
Identification, substrate specificity, and inhibition of the

Streptococcus pneumoniae

β-ketoacyl-

acyl carrier protein synthase III (FabH).

J. Biol. Chem.

276 (2001) 30024–30030. [PMID:

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11375394

]

4. Choi, K.H., Kremer, L., Besra, G.S. and Rock, C.O. Identification and substrate specificity of β-

ketoacyl (acyl carrier protein) synthase III (mtFabH) from

Mycobacterium tuberculosis

J. Biol.

Chem.

275 (2000) 28201–28207. [PMID:

10840036

]

5. Qiu, X., Choudhry, A.E., Janson, C.A., Grooms, M., Daines, R.A., Lonsdale, J.T. and Khandekar,

S.S. Crystal structure and substrate specificity of the β-ketoacyl-acyl carrier protein synthase III
(FabH) from

Staphylococcus aureus

Protein Sci.

14 (2005) 2087–2094. [PMID:

15987898

]

6. Li, Y., Florova, G. and Reynolds, K.A. Alteration of the fatty acid profile of

Streptomyces

coelicolor

by replacement of the initiation enzyme 3-ketoacyl acyl carrier protein synthase III

(FabH).

J. Bacteriol.

187 (2005) 3795–3799. [PMID:

15901703

]

7. Cronan, J.E., Jr. and Rock, C.O. Biosynthesis of membrane lipids. In: Neidhardt, F.C. (Ed.),

Escherichia coli and Salmonella: Cellular and Molecular Biology

, 2nd edn, vol. 1, ASM Press,

Washington, DC, 1996, pp. 612–636.

[EC 2.3.1.180 created 2006]

EC 2.3.1.181

Common name: lipoyl(octanoyl) transferase

Reaction: octanoyl-[acyl-carrier-protein] + protein = protein 6-

-(octanoyl)lysine + acyl carrier protein

Glossary:

lipoyl group

Other name(s): LipB; lipoyl (octanoyl)-[acyl-carrier-protein]-protein

-lipoyltransferase; lipoyl (octanoyl)-acyl carrier

protein:protein transferase; lipoate/octanoate transferase; lipoyltransferase; octanoyl-[acyl carrier
protein]-protein

-octanoyltransferase; lipoyl(octanoyl)transferase

Systematic name: octanoyl-[acyl-carrier-protein]:protein

-octanoyltransferase

Comments: This is the first committed step in the biosynthesis of lipoyl cofactor. Lipoylation is essential for the

function of several key enzymes involved in oxidative metabolism, as it converts apoprotein into the
biologically active holoprotein. Examples of such lipoylated proteins include pyruvate
dehydrogenase (E

domain), 2-oxoglutarate dehydrogenase (E

domain), the branched-chain

oxoacid dehydrogenases

and the

glycine cleavage system

(H protein) [2,3]. Lipoyl-ACP can also

act as a substrate [4] although octanoyl-ACP is likely to be the true substrate [6] . The other
enzyme involved in the biosynthesis of lipoyl cofactor is

EC 2.8.1.8

, lipoyl synthase. An alternative

lipoylation pathway involves

EC 2.7.7.63

, lipoate—protein ligase, which can lipoylate apoproteins

using exogenous lipoic acid (or its analogues).

References: 1. Nesbitt, N.M., Baleanu-Gogonea, C., Cicchillo, R.M., Goodson, K., Iwig, D.F., Broadwater, J.A.,

Haas, J.A., Fox, B.G. and Booker, S.J. Expression, purification, and physical characterization of

Escherichia coli

lipoyl(octanoyl)transferase.

Protein Expr. Purif.

39 (2005) 269–282. [PMID:

15642479

]

2. Vanden Boom, T.J., Reed, K.E. and Cronan, J.E., Jr. Lipoic acid metabolism in

Escherichia coli

isolation of null mutants defective in lipoic acid biosynthesis, molecular cloning and
characterization of the

E. coli

lip

locus, and identification of the lipoylated protein of the glycine

cleavage system.

J. Bacteriol.

173 (1991) 6411–6420. [PMID:

1655709

]

3. Jordan, S.W. and Cronan, J.E., Jr. A new metabolic link. The acyl carrier protein of lipid

synthesis donates lipoic acid to the pyruvate dehydrogenase complex in

Escherichia coli

and

mitochondria.

J. Biol. Chem.

272 (1997) 17903–17906. [PMID:

9218413

]

4. Zhao, X., Miller, J.R., Jiang, Y., Marletta, M.A. and Cronan, J.E. Assembly of the covalent linkage

between lipoic acid and its cognate enzymes.

Chem. Biol.

10 (2003) 1293–1302. [PMID:

14700636

]

5. Wada, M., Yasuno, R., Jordan, S.W., Cronan, J.E., Jr. and Wada, H. Lipoic acid metabolism in

Arabidopsis thaliana

: cloning and characterization of a cDNA encoding lipoyltransferase.

Plant

Cell Physiol.

42 (2001) 650–656. [PMID:

11427685

]

6. Perham, R.N. Swinging arms and swinging domains in multifunctional enzymes: catalytic

machines for multistep reactions.

Annu. Rev. Biochem.

69 (2000) 961–1004. [PMID:

10966480

]

[EC 2.3.1.181 created 2006]

*EC 2.4.1.195

Common name:

-hydroxythioamide

-β-glucosyltransferase

Reaction: UDP-glucose +

-hydroxy-2-phenylethanethioamide = UDP + desulfoglucotropeolin

For diagram of glucotropeolin biosynthesis,

click here

Other name(s): desulfoglucosinolate-uridine diphosphate glucosyltransferase; uridine diphosphoglucose-

thiohydroximate glucosyltransferase; thiohydroximate β-

-glucosyltransferase;

UDPG:thiohydroximate glucosyltransferase; thiohydroximate

-glucosyltransferase; thiohydroximate

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glucosyltransferase; UDP-glucose:thiohydroximate

-β-

-glucosyltransferase

Systematic name: UDP-glucose:

-hydroxy-2-phenylethanethioamide

-β-

-glucosyltransferase

Comments: Involved with

EC 2.8.2.24

, desulfoglucosinolate sulfotransferase, in the biosynthesis of

thioglucosides in cruciferous plants.

Links to other databases:

BRENDA

ERGO

EXPASY

IUBMB

KEGG

, CAS registry number: 9068-14-8

References: 1. Jain, J.C., Reed, D.W., Groot Wassink, J.W.D. and Underhill, E.W. A radioassay of enzymes

catalyzing the glucosylation and sulfation steps of glucosinolate biosynthesis in

Brassica

species.

Anal. Biochem.

178 (1989) 137–140. [PMID:

2524977

]

2. Reed, D.W., Davin, L., Jain, J.C., Deluca, V., Nelson, L. and Underhill, E.W. Purification and

properties of UDP-glucose:thiohydroximate glucosyltransferase from

Brassica napus

seedlings.

Arch. Biochem. Biophys.

305 (1993) 526–532. [PMID:

8373190

]

3. Fahey, J.W., Zalcmann, A.T. and Talalay, P. The chemical diversity and distribution of

glucosinolates and isothiocyanates among plants.

Phytochemistry

56 (2001) 5–51. [PMID:

11198818

]

4. Grubb, C.D., Zipp, B.J., Ludwig-MÃ¼ller, J., Masuno, M.N., Molinski, T.F. and Abel, S.

Arabidopsis glucosyltransferase UGT74B1 functions in glucosinolate biosynthesis and auxin
homeostasis.

Plant J.

40 (2004) 893–908.

[EC 2.4.1.195 created 1992, modified 2006]

EC 2.4.1.243

Common name: 6

-fructosyltransferase

Reaction: [1-β-

-fructofuranosyl-(2→1)-]

α-

-glucopyranoside + [1-β-

-fructofuranosyl-(2→1)-]

α-

glucopyranoside = [1-β-

-fructofuranosyl-(2→1)-]

α-

-glucopyranoside + [1-β-

-fructofuranosyl-

(2→1)-]

β-

-fructofuranosyl-(2→6)-α-

-glucopyranoside (

> 0;

≥ 0)

Other name(s): fructan:fructan 6

-fructosyltransferase; 1

(1-β-

-fructofuranosyl)

sucrose:1

(1-β-

fructofuranosyl)

sucrose 6

-fructosyltransferase; 6

-FFT; 6

-FT; 6

-fructotransferase

Systematic name: 1

-oligo[β-

-fructofuranosyl-(2→1)-]sucrose 6

-β-

-fructotransferase

Comments: This enzyme catalyses the transfer of the terminal (2→1)-linked β-

-fructosyl group of a mono- or

oligosaccharide substituent on

-1 of the fructose residue of sucrose onto

-6 of its glucose

residue [1]. For example, if 1-kestose [1

-(β-

-fructofuranosyl)sucrose] is both the donor and

recipient in the reaction shown above, i.e., if

= 1 and

= 1, then the products will be sucrose and

-di-β-

-fructofuranosylsucrose. In this notation, the superscripts F and G are used to specify

whether the fructose or glucose residue of the sucrose carries the substituent. Alternatively, this
may be indicated by the presence and/or absence of primes (see

http://www.chem.qmul.ac.uk/iupac/2carb/36.html#362

). Sucrose cannot be a donor substrate in the

reaction (i.e.

cannot be zero) and inulin cannot act as an acceptor. Side reactions catalysed are

transfer of a β-

-fructosyl group between compounds of the structure 1

-(1-β-

-fructofuranosyl)

-(1-β-

-fructofuranosyl)

sucrose, where

≥ 0 and

= 1 for the donor, and

≥ 0 and

≥ 0 for

the acceptor.

References: 1. Shiomi, N. Purification and characterisation of 6

-fructosyltransferase from the roots of

asparagus (

Asparagus officinalis

L.).

Carbohydr. Res.

96 (1981) 281–292.

2. Shiomi, N. Reverse reaction of fructosyl transfer catalysed by asparagus 6

-fructosyltransferase.

Carbohydr. Res.

106 (1982) 166–169.

3. Shiomi, N. and Ueno, K. Cloning and expression of genes encoding fructosyltransferases from

higher plants in food technology.

J. Appl. Glycosci.

51 (2004) 177–183.

4. Ueno, K., Onodera, S., Kawakami, A., Yoshida, M. and Shiomi, N. Molecular characterization

and expression of a cDNA encoding fructan:fructan 6

-fructosyltransferase from asparagus

(

Asparagus officinalis

New Phytol.

165 (2005) 813–824. [PMID:

15720693

]

[EC 2.4.1.243 created 2006]

EC 2.4.1.244

Common name:

-acetyl-β-glucosaminyl-glycoprotein 4-β-

-acetylgalactosaminyltransferase

Reaction: UDP-

-acetyl-

-galactosamine +

-acetyl-β-

-glucosaminyl group = UDP +

-acetyl-β-

galactosaminyl-(1→4)-

-acetyl-β-

-glucosaminyl group

Glossary:

'-diacetyllactosediamine =

-acetyl-β-

-galactosaminyl-(1→4)-

-acetyl-

-glucosamine

Other name(s): β1,4-

-acetylgalactosaminyltransferase III; β4GalNAc-T3; β1,4-

-acetylgalactosaminyltransferase

IV; β4GalNAc-T4

06/27/2006 05:11 PM

The Enzyme Database: New Enzymes

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http://www.enzyme-database.org/newenz.php?sp=off

Systematic name: UDP-

-acetyl-

-galactosamine:

-acetyl-

-glucosaminyl-group β-1,4-

acetylgalactosaminyltransferase

Comments: The enzyme from human can transfer

-acetyl-

-galactosamine (GalNAc) to

-glycan and

glycan substrates that have

-acetyl-

-glucosamine (GlcNAc) but not

-glucuronic acid (GlcUA) at

their non-reducing end. The

-acetyl-β-

-glucosaminyl group is normally on a core oligosaccharide

although benzyl glycosides have been used in enzyme-characterization experiments. Some
glycohormones, e.g. lutropin and thyrotropin contain the

-glycan structure containing the

-acetyl-

β-

-galactosaminyl-(1→4)-

-acetyl-β-

-glucosaminyl group.

References: 1. Sato, T., Gotoh, M., Kiyohara, K., Kameyama, A., Kubota, T., Kikuchi, N., Ishizuka, Y., Iwasaki,

H., Togayachi, A., Kudo, T., Ohkura, T., Nakanishi, H. and Narimatsu, H. Molecular cloning and
characterization of a novel human β1,4-

-acetylgalactosaminyltransferase, β4GalNAc-T3,

responsible for the synthesis of

'-diacetyllactosediamine, GalNAc β1-4GlcNAc.

J. Biol.

Chem.

278 (2003) 47534–47544. [PMID:

12966086

]

2. Gotoh, M., Sato, T., Kiyohara, K., Kameyama, A., Kikuchi, N., Kwon, Y.D., Ishizuka, Y., Iwai, T.,

Nakanishi, H. and Narimatsu, H. Molecular cloning and characterization of β1,4-

acetylgalactosaminyltransferases IV synthesizing

'-diacetyllactosediamine.

FEBS Lett.

562

(2004) 134–140. [PMID:

15044014

]

[EC 2.4.1.244 created 2006]

*EC 2.6.1.52

Common name: phosphoserine transaminase

Reaction: (1)

-phospho-

-serine + 2-oxoglutarate = 3-phosphonooxypyruvate +

-glutamate

(2) 4-phosphonooxy-

-threonine + 2-oxoglutarate = (3

)-3-hydroxy-2-oxo-4-

phosphonooxybutanoate +

-glutamate

For diagram of reaction,

click here

, for mechanism,

click here

and for diagram of pyridoxal

biosynthesis,

click here

Other name(s): PSAT; phosphoserine aminotransferase; 3-phosphoserine aminotransferase; hydroxypyruvic

phosphate-glutamic transaminase;

-phosphoserine aminotransferase; phosphohydroxypyruvate

transaminase; phosphohydroxypyruvic-glutamic transaminase; 3-

-phospho-

-serine:2-

oxoglutarate aminotransferase; SerC; PdxC; 3PHP transaminase

Systematic name:

-phospho-

-serine:2-oxoglutarate aminotransferase

Comments: A pyridoxal-phosphate protein. This enzyme catalyses the second step in the phosphorylated

pathway of serine biosynthesis in

Escherichia coli

[2,3]. It also catalyses the third step in the

biosynthesis of the coenzyme pyridoxal 5′-phosphate in

Escherichia coli

(using Reaction 2 above)

[3]. In

Escherichia coli

, pyridoxal 5′-phosphate is synthesized de novo by a pathway that involves

EC 1.2.1.72

(erythrose-4-phosphate dehydrogenase),

EC 1.1.1.290

(4-phosphoerythronate

dehydrogenase), EC 2.6.1.52 (phosphoserine transaminase),

EC 1.1.1.262

(4-hydroxythreonine-4-

phosphate dehydrogenase),

EC 2.6.99.2

(pyridoxine 5′-phosphate synthase) and

EC 1.4.3.5

(with

pyridoxine 5′-phosphate as substrate). Pyridoxal phosphate is the cofactor for both activities and
therefore seems to be involved in its own biosynthesis [4]. Non-phosphorylated forms of serine and
threonine are not substrates [4].

Links to other databases:

BRENDA

ERGO

EXPASY

GTD

IUBMB

KEGG

PDB

, CAS registry number: 9030-90-4

References: 1. Hirsch, H. and Greenberg, D.M. Studies on phosphoserine aminotransferase of sheep brain.

Biol. Chem.

242 (1967) 2283–2287. [PMID:

6022873

]

2. Pizer, L.I. The pathway and control of serine biosynthesis in

Escherichia coli

J. Biol. Chem.

238

(1963) 3934–3944. [PMID:

14086727

]

3. Zhao, G. and Winkler, M.E. A novel α-ketoglutarate reductase activity of the

serA

-encoded 3-

phosphoglycerate dehydrogenase of

Escherichia coli

K-12 and its possible implications for

human 2-hydroxyglutaric aciduria.

J. Bacteriol.

178 (1996) 232–239. [PMID:

8550422

]

4. Drewke, C., Klein, M., Clade, D., Arenz, A., Müller, R. and Leistner, E. 4-

-phosphoryl-

threonine, a substrate of the

pdxC

(

serC

) gene product involved in vitamin B

biosynthesis.

FEBS Lett.

390 (1996) 179–182. [PMID:

8706854

]

5. Zhao, G. and Winkler, M.E. 4-Phospho-hydroxy-

-threonine is an obligatory intermediate in

pyridoxal 5′-phosphate coenzyme biosynthesis in

Escherichia coli

K-12.

FEMS Microbiol. Lett.

135 (1996) 275–280. [PMID:

8595869

]

[EC 2.6.1.52 created 1972, modified 2006]

*EC 2.6.1.76

Common name: diaminobutyrate—2-oxoglutarate transaminase

Reaction:

-2,4-diaminobutanoate + 2-oxoglutarate =

-aspartate 4-semialdehyde +

-glutamate

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The Enzyme Database: New Enzymes

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http://www.enzyme-database.org/newenz.php?sp=off

For diagram of ectoine biosynthesis,

click here

Other name(s):

-2,4-diaminobutyrate:2-ketoglutarate 4-aminotransferase; 2,4-diaminobutyrate 4-aminotransferase;

diaminobutyrate aminotransferase; DABA aminotransferase; DAB aminotransferase; EctB;
diaminibutyric acid aminotransferase;

-2,4-diaminobutyrate:2-oxoglutarate 4-aminotransferase

Systematic name:

-2,4-diaminobutanoate:2-oxoglutarate 4-aminotransferase

Comments: A pyridoxal-phosphate protein that requires potassium for activity [4]. In the proteobacterium

Acinetobacter baumannii

, this enzyme is a product of the

ddc

gene that also encodes EC 4.1.1.85,

diaminobutyrate decarboxylase. Differs from

EC 2.6.1.46

, diaminobutyrate—pyruvate transaminase,

which has pyruvate as the amino-group acceptor. This is the first enzyme in the ectoine-
biosynthesis pathway, the other enzymes involved being

EC 2.3.1.178

, diaminobutyrate

acetyltransferase and

EC 4.2.1.108

, ectoine synthase [3,4].

Links to other databases:

BRENDA

ERGO

EXPASY

IUBMB

KEGG

, CAS registry number: 196622-96-5

References: 1. Ikai, H. and Yamamoto, S. Identification and analysis of a gene encoding

-2,4-

diaminobutyrate:2-ketoglutarate 4-aminotransferase involved in the 1,3-diaminopropane
production pathway in

Acinetobacter baumannii

J. Bacteriol.

179 (1997) 5118–5125. [PMID:

9260954

]

2. Ikai, H. and Yamamoto, S. Two genes involved in the 1,3-diaminopropane production pathway in

Haemophilus influenzae

Biol. Pharm. Bull.

21 (1998) 170–173. [PMID:

9514614

]

3. Peters, P., Galinski, E.A. and Truper, H.G. The biosynthesis of ectoine.

FEMS Microbiol. Lett.

(1990) 157–162.

4. Ono, H., Sawada, K., Khunajakr, N., Tao, T., Yamamoto, M., Hiramoto, M., Shinmyo, A., Takano,

M. and Murooka, Y. Characterization of biosynthetic enzymes for ectoine as a compatible solute
in a moderately halophilic eubacterium,

Halomonas elongata

J. Bacteriol.

181 (1999) 91–99.

[PMID:

9864317

]

5. Kuhlmann, A.U. and Bremer, E. Osmotically regulated synthesis of the compatible solute ectoine

Bacillus pasteurii

and related

Bacillus

spp.

Appl. Environ. Microbiol.

68 (2002) 772–783.

[PMID:

11823218

]

6. Louis, P. and Galinski, E.A. Characterization of genes for the biosynthesis of the compatible

solute ectoine from

Marinococcus halophilus

and osmoregulated expression in

Escherichia coli

Microbiology

143 (1997) 1141–1149. [PMID:

9141677

]

[EC 2.6.1.76 created 2000, modified 2006]

EC 2.6.1.81

Common name: succinylornithine transaminase

Reaction: 2-

-succinyl-

-ornithine + 2-oxoglutarate =

-succinyl-

-glutamate 5-semialdehyde +

-glutamate

For diagram of arginine catabolism,

click here

Other name(s): succinylornithine aminotransferase;

-succinylornithine 5-aminotransferase; AstC; SOAT;

succinyl-

-ornithine:2-oxoglutarate 5-aminotransferase

Systematic name: 2-

-succinyl-

-ornithine:2-oxoglutarate 5-aminotransferase

Comments: A pyridoxal-phosphate protein. Also acts on 2-

-acetyl-

-ornithine and

-ornithine, but more slowly

[3]. In

Pseudomonas aeruginosa

, the arginine-inducible succinylornithine transaminase,

acetylornithine transaminase (

EC 2.6.1.11

) and ornithine aminotransferase (

EC 2.6.1.13

) activities

are catalysed by the same enzyme, but this is not the case in all species [5]. This is the third
enzyme in the arginine succinyltransferase (AST) pathway for the catabolism of arginine [1]. This
pathway converts the carbon skeleton of arginine into glutamate, with the concomitant production of
ammonia and conversion of succinyl-CoA into succinate and CoA. The five enzymes involved in
this pathway are

EC 2.3.1.109

(arginine

-succinyltransferase),

EC 3.5.3.23

(

-succinylarginine

dihydrolase), EC 2.6.1.81 (succinylornithine transaminase),

EC 1.2.1.71

(succinylglutamate-

semialdehyde dehydrogenase) and

EC 3.5.1.96

(succinylglutamate desuccinylase) [3, 6].

References: 1. Vander Wauven, C. and Stalon, V. Occurrence of succinyl derivatives in the catabolism of

arginine in

Pseudomonas cepacia

J. Bacteriol.

164 (1985) 882–886. [PMID:

2865249

]

2. Schneider, B.L., Kiupakis, A.K. and Reitzer, L.J. Arginine catabolism and the arginine

succinyltransferase pathway in

Escherichia coli

J. Bacteriol.

180 (1998) 4278–4286. [PMID:

9696779

]

3. Cunin, R., Glansdorff, N., Pierard, A. and Stalon, V. Biosynthesis and metabolism of arginine in

bacteria.

Microbiol. Rev.

50 (1986) 314–352. [PMID:

3534538

]

4. Itoh, Y. Cloning and characterization of the

aru

genes encoding enzymes of the catabolic

arginine succinyltransferase pathway in

Pseudomonas aeruginosa

J. Bacteriol.

179 (1997)

7280–7290. [PMID:

9393691

]

5. Stalon, V., Vander Wauven, C., Momin, P. and Legrain, C. Catabolism of arginine, citrulline and

ornithine by

Pseudomonas

and related bacteria.

J. Gen. Microbiol.

133 (1987) 2487–2495.

06/27/2006 05:11 PM

The Enzyme Database: New Enzymes

Page 24 of 48

http://www.enzyme-database.org/newenz.php?sp=off

[PMID:

3129535

]

[EC 2.6.1.81 created 2006]

EC 2.6.99.2

Common name: pyridoxine 5′-phosphate synthase

Reaction: 1-deoxy-

-xylulose 5-phosphate + 3-amino-2-oxopropyl phosphate = pyridoxine 5′-phosphate +

phosphate + 2 H

For diagram of pyridoxal biosynthesis,

click here

Other name(s): pyridoxine 5-phosphate phospho lyase; PNP synthase; PdxJ

Systematic name: 1-deoxy-

-xylulose-5-phosphate:3-amino-2-oxopropyl phosphate 3-amino-2-oxopropyltransferase

(phosphate-hydrolysing; cyclizing)

Comments: In

Escherichia coli

, the coenzyme pyridoxal 5′-phosphate is synthesized de novo by a pathway that

involves

EC 1.2.1.72

(erythrose-4-phosphate dehydrogenase),

EC 1.1.1.290

(4-

phosphoerythronate dehydrogenase),

EC 2.6.1.52

(phosphoserine transaminase),

EC 1.1.1.262

(4-

hydroxythreonine-4-phosphate dehydrogenase), EC 2.6.99.2 (pyridoxine 5′-phosphate synthase)
and

EC 1.4.3.5

(with pyridoxine 5′-phosphate as substrate). 1-Deoxy-

-xylulose cannot replace 1-

deoxy-

-xylulose 5-phosphate as a substrate [3].

References: 1. Garrido-Franco, M. Pyridoxine 5′-phosphate synthase: de novo synthesis of vitamin B

and

beyond.

Biochim. Biophys. Acta

1647 (2003) 92–97. [PMID:

12686115

]

2. Garrido-Franco, M., Laber, B., Huber, R. and Clausen, T. Enzyme-ligand complexes of

pyridoxine 5′-phosphate synthase: implications for substrate binding and catalysis.

J. Mol. Biol.

321 (2002) 601–612. [PMID:

12206776

]

3. Laber, B., Maurer, W., Scharf, S., Stepusin, K. and Schmidt, F.S. Vitamin B

biosynthesis:

formation of pyridoxine 5′-phosphate from 4-(phosphohydroxy)-

-threonine and 1-deoxy-

xylulose-5-phosphate by PdxA and PdxJ protein.

FEBS Lett.

449 (1999) 45–48. [PMID:

10225425

]

4. Franco, M.G., Laber, B., Huber, R. and Clausen, T. Structural basis for the function of pyridoxine

5′-phosphate synthase.

Structure

9 (2001) 245–253. [PMID:

11286891

]

[EC 2.6.99.2 created 2006]

*EC 2.7.1.151

Common name: inositol-polyphosphate multikinase

Reaction: (1) ATP + 1

myo

-inositol 1,4,5-trisphosphate = ADP + 1

myo

-inositol 1,4,5,6-tetrakisphosphate

(2) ATP + 1

myo

-inositol 1,4,5,6-tetrakisphosphate = ADP + 1

myo

-inositol 1,3,4,5,6-

pentakisphosphate

For diagram of

myo

-inositol-phosphate metabolism,

click here

Other name(s): IpK2; IP3/IP4 6-/3-kinase; IP3/IP4 dual-specificity 6-/3-kinase; IpmK; ArgRIII; AtIpk2α; AtIpk2β;

inositol polyphosphate 6-/3-/5-kinase

Systematic name: ATP:1

myo

-inositol-1,4,5-trisphosphate 6-phosphotransferase

Comments: This enzyme also phosphorylates Ins(1,4,5)

to Ins(1,3,4,5)

, Ins(1,3,4,5)

to Ins(1,3,4,5,6)

and Ins(1,3,4,5,6)

to Ins(PP)

, isomer unknown. The enzyme from the plant

Arabidopsis

thaliana

can also phosphorylate Ins(1,3,4,6)

and Ins(1,2,3,4,6)

at the

-5-position to produce

1,3,4,5,6-pentakisphosphate and inositol hexakisphosphate (Ins

), respectively [3]. Yeast produce

Ins

from Ins(1,4,5)

by the actions of this enzyme and

EC 2.7.1.158

, inositol-

pentakisphosphate 2-kinase [4].

Links to other databases:

BRENDA

ERGO

EXPASY

IUBMB

KEGG

References: 1. Saiardi, A., Erdjument-Bromage, H., Snowman, A.M., Tempst, P. and Snyder, S.H. Synthesis of

diphosphoinositol pentakisphosphate by a newly identified family of higher inositol polyphosphate
kinases.

Curr. Biol.

9 (1999) 1323–1326. [PMID:

10574768

]

2. Odom, A.R., Stahlberg, A., Wente, S.R. and York, J.D. A role for nuclear inositol 1,4,5-

trisphosphate kinase in transcriptional control.

Science

287 (2000) 2026–2029. [PMID:

10720331

]

3. Stevenson-Paulik, J., Odom, A.R. and York, J.D. Molecular and biochemical characterization of

two plant inositol polyphosphate 6-/3-/5-kinases.

J. Biol. Chem.

277 (2002) 42711–42718.

[PMID:

12226109

]

4. Verbsky, J.W., Chang, S.C., Wilson, M.P., Mochizuki, Y. and Majerus, P.W. The pathway for the

production of inositol hexakisphosphate in human cells.

J. Biol. Chem.

280 (2005) 1911–1920.

[PMID:

15531582

]

06/27/2006 05:11 PM

The Enzyme Database: New Enzymes

Page 25 of 48

http://www.enzyme-database.org/newenz.php?sp=off

[EC 2.7.1.151 created 2002, modified 2006]

EC 2.7.1.158

Common name: inositol-pentakisphosphate 2-kinase

Reaction: ATP + 1

myo

-inositol 1,3,4,5,6-pentakisphosphate = ADP + 1

myo

-inositol hexakisphosphate

Other name(s): IP5 2-kinase; Gsl1p; Ipk1p; inositol polyphosphate kinase; inositol 1,3,4,5,6-pentakisphosphate 2-

kinase; Ins(1,3,4,5,6)

2-kinase

Systematic name: ATP:1

myo

-inositol 1,3,4,5,6-pentakisphosphate 2-phosphotransferase

Comments: The enzyme can also use Ins(1,4,5,6)

[2] and Ins(1,4,5)

[3] as substrate. Inositol

hexakisphosphate (phytate) accumulates in storage protein bodies during seed development and,
when hydrolysed, releases stored nutrients to the developing seedling before the plant is capable
of absorbing nutrients from its environment [5].

References: 1. York, J.D., Odom, A.R., Murphy, R., Ives, E.B. and Wente, S.R. A phospholipase C-dependent

inositol polyphosphate kinase pathway required for efficient messenger RNA export.

Science

285

(1999) 96–100. [PMID:

10390371

]

2. Phillippy, B.Q., Ullah, A.H. and Ehrlich, K.C. Purification and some properties of inositol

1,3,4,5,6-Pentakisphosphate 2-kinase from immature soybean seeds.

J. Biol. Chem.

269 (1994)

28393–28399. [PMID:

7961779

]

3. Phillippy, B.Q., Ullah, A.H. and Ehrlich, K.C. Additions and corrections to Purification and some

properties of inositol 1,3,4,5,6-pentakisphosphate 2-kinase from immature soybean seeds.

Biol. Chem.

270 (1997) 7782 only.

4. Ongusaha, P.P., Hughes, P.J., Davey, J. and Michell, R.H. Inositol hexakisphosphate in

Schizosaccharomyces pombe

: synthesis from Ins(1,4,5)

and osmotic regulation.

Biochem. J.

335 (1998) 671–679. [PMID:

9794810

]

5. Miller, A.L., Suntharalingam, M., Johnson, S.L., Audhya, A., Emr, S.D. and Wente, S.R.

Cytoplasmic inositol hexakisphosphate production is sufficient for mediating the Gle1-mRNA
export pathway.

J. Biol. Chem.

279 (2004) 51022–51032. [PMID:

15459192

]

6. Stevenson-Paulik, J., Odom, A.R. and York, J.D. Molecular and biochemical characterization of

two plant inositol polyphosphate 6-/3-/5-kinases.

J. Biol. Chem.

277 (2002) 42711–42718.

[PMID:

12226109

]

[EC 2.7.1.158 created 2006]

EC 2.7.1.159

Common name: inositol-1,3,4-trisphosphate 5/6-kinase

Reaction: (1) ATP + 1

myo

-inositol 1,3,4-trisphosphate = ADP + 1

myo

-inositol 1,3,4,5-tetrakisphosphate

(2) ATP + 1

myo

-inositol 1,3,4-trisphosphate = ADP + 1

myo

-inositol 1,3,4,6-tetrakisphosphate

Other name(s): Ins(1,3,4)

5/6-kinase; inositol trisphosphate 5/6-kinase

Systematic name: ATP:1

myo

-inositol 1,3,4-trisphosphate 5-phosphotransferase

Comments: In humans, this enzyme, along with

EC 2.7.1.127

(inositol-trisphosphate 3-kinase),

EC 2.7.1.140

(inositol-tetrakisphosphate 5-kinase) and

EC 2.7.1.158

(inositol pentakisphosphate 2-kinase) is

involved in the production of inositol hexakisphosphate (Ins

). Ins

is involved in many cellular

processes, including mRNA export from the nucleus [2]. Yeasts do not have this enzyme, so
produce Ins

from Ins(1,4,5)

by the actions of

EC 2.7.1.151

(inositol-polyphosphate

multikinase) and

EC 2.7.1.158

(inositol-pentakisphosphate 2-kinase) [2].

References: 1. Wilson, M.P. and Majerus, P.W. Isolation of inositol 1,3,4-trisphosphate 5/6-kinase, cDNA

cloning and expression of the recombinant enzyme.

J. Biol. Chem.

271 (1996) 11904–11910.

[PMID:

8662638

]

2. Verbsky, J.W., Chang, S.C., Wilson, M.P., Mochizuki, Y. and Majerus, P.W. The pathway for the

production of inositol hexakisphosphate in human cells.

J. Biol. Chem.

280 (2005) 1911–1920.

[PMID:

15531582

]

3. Miller, G.J., Wilson, M.P., Majerus, P.W. and Hurley, J.H. Specificity determinants in inositol

polyphosphate synthesis: crystal structure of inositol 1,3,4-trisphosphate 5/6-kinase.

Mol. Cell.

(2005) 201–212. [PMID:

15837423

]

[EC 2.7.1.159 created 2006]

EC 2.7.4.22

Common name: UMP kinase

06/27/2006 05:11 PM

The Enzyme Database: New Enzymes

Page 26 of 48

http://www.enzyme-database.org/newenz.php?sp=off

Reaction: ATP + UMP = ADP + UDP

Other name(s): uridylate kinase; UMPK; uridine monophosphate kinase; PyrH; UMP-kinase; SmbA

Systematic name: ATP:UMP phosphotransferase

Comments: This enzyme is strictly specific for UMP as substrate and is used by prokaryotes in the de novo

synthesis of pyrimidines, in contrast to eukaryotes, which use the dual-specificity enzyme
UMP/CMP kinase (

EC 2.7.4.14

) for the same purpose [2]. This enzyme is the subject of feedback

regulation, being inhibited by UTP and activated by GTP [1].

References: 1. Serina, L., Blondin, C., Krin, E., Sismeiro, O., Danchin, A., Sakamoto, H., Gilles, A.M. and Bârzu,

Escherichia coli

UMP-kinase, a member of the aspartokinase family, is a hexamer regulated

by guanine nucleotides and UTP.

Biochemistry

34 (1995) 5066–5074. [PMID:

7711027

]

2. Marco-Marín, C., Gil-Ortiz, F. and Rubio, V. The crystal structure of

Pyrococcus furiosus

UMP

kinase provides insight into catalysis and regulation in microbial pyrimidine nucleotide
biosynthesis.

J. Mol. Biol.

352 (2005) 438–454. [PMID:

16095620

]

[EC 2.7.4.22 created 2006]

EC 2.7.7.63

Common name: lipoate—protein ligase

Reaction: (1) ATP + lipoate = diphosphate + lipoyl-AMP

(2) lipoyl-AMP + apoprotein = protein 6-

-(lipoyl)lysine + AMP

Other name(s): LplA; lipoate protein ligase; lipoate-protein ligase A; LPL; LPL-B

Systematic name: ATP:lipoate adenylyltransferase

Comments: Requires Mg

. Both 6

- and 6

-lipoates can act as substrates but there is a preference for the

naturally occurring

-form. Selenolipoate, i.e. 5-(1,2-diselenolan-3-yl)pentanoic acid, and 6-

sulfanyloctanoate can also act as substrates, but more slowly [2]. This enzyme is responsible for
lipoylation in the presence of exogenous lipoic acid [7]. Lipoylation is essential for the function of
several key enzymes involved in oxidative metabolism, including pyruvate dehydrogenase (E

domain), 2-oxoglutarate dehydrogenase (E

domain), the branched-chain

2-oxoacid

dehydrogenases

and the

glycine cleavage system

(H protein) [6]. This enzyme attaches lipoic acid

to the lipoyl domains of these proteins, converting apoproteins into holoproteins. It is likely that an
alternative pathway, involving

EC 2.3.1.181

, lipoyl(octanoyl) transferase and

EC 2.8.1.8

, lipoyl

synthase, is the normal route for lipoylation [7].

References: 1. Morris, T.W., Reed, K.E. and Cronan, J.E., Jr. Identification of the gene encoding lipoate-protein

ligase A of

Escherichia coli

. Molecular cloning and characterization of the

lplA

gene and gene

product.

J. Biol. Chem.

269 (1994) 16091–16100. [PMID:

8206909

]

2. Green, D.E., Morris, T.W., Green, J., Cronan, J.E., Jr. and Guest, J.R. Purification and properties

of the lipoate protein ligase of

Escherichia

coli.

Biochem. J.

309 (1995) 853–862. [PMID:

7639702

]

3. Zhao, X., Miller, J.R., Jiang, Y., Marletta, M.A. and Cronan, J.E. Assembly of the covalent linkage

between lipoic acid and its cognate enzymes.

Chem. Biol.

10 (2003) 1293–1302. [PMID:

14700636

]

4. Kim do, J., Kim, K.H., Lee, H.H., Lee, S.J., Ha, J.Y., Yoon, H.J. and Suh, S.W. Crystal structure

of lipoate-protein ligase A bound with the activated intermediate: insights into interaction with
lipoyl domains.

J. Biol. Chem.

280 (2005) 38081–38089. [PMID:

16141198

]

5. Fujiwara, K., Toma, S., Okamura-Ikeda, K., Motokawa, Y., Nakagawa, A. and Taniguchi, H.

Crystal structure of lipoate-protein ligase A from

Escherichia coli

. Determination of the lipoic

acid-binding site.

J. Biol. Chem.

280 (2005) 33645–33651. [PMID:

16043486

]

6. Jordan, S.W. and Cronan, J.E., Jr. A new metabolic link. The acyl carrier protein of lipid

synthesis donates lipoic acid to the pyruvate dehydrogenase complex in

Escherichia coli

and

mitochondria.

J. Biol. Chem.

272 (1997) 17903–17906. [PMID:

9218413

]

7. Perham, R.N. Swinging arms and swinging domains in multifunctional enzymes: catalytic

machines for multistep reactions.

Annu. Rev. Biochem.

69 (2000) 961–1004. [PMID:

10966480

]

[EC 2.7.7.63 created 2006]

*EC 2.8.1.6

Common name: biotin synthase

Reaction: dethiobiotin + sulfur + 2

-adenosyl-

-methionine = biotin + 2

-methionine + 2 5′-deoxyadenosine

Systematic name: dethiobiotin:sulfur sulfurtransferase

Comments: This single-turnover enzyme is a member of the 'AdoMet radical ' (radical SAM) family, all members

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of which produce the 5′-deoxyadenosin-5′-yl radical and methionine from AdoMet [i.e.

adenosylmethionine, or

-5′-deoxyadenosin-5′-yl)methionine], by the addition of an electron from

an iron-sulfur centre. The enzyme has both a [2Fe-2S] and a [4Fe-4S] centre, and the latter is
believed to donate the electron. Two molecules of AdoMet are converted into radicals; these
activate positions 6 and 9 of dethiobiotin by abstracting a hydrogen atom from each, and thereby
forming 5′-deoxyadenosine. Sulfur insertion into dethiobiotin at C-6 takes place with retention of
configuration [3]. The sulfur donor has not been identified to date — it is neither elemental sulfur nor
from AdoMet, but it may be from the [2Fe-2S] centre [4].

Links to other databases:

BRENDA

ERGO

EXPASY

IUBMB

KEGG

PDB

References: 1. Shiuan, D. and Campbell, A. Transcriptional regulation and gene arrangement of

Escherichia

coli

Citrobacter freundii

and

Salmonella typhimurium

biotin operons.

Gene

67 (1988) 203–211.

[PMID:

2971595

]

2. Zhang, S., Sanyal, I., Bulboaca, G.H., Rich, A. and Flint, D.H. The gene for biotin synthase from

Saccharomyces cerevisiae

: cloning, sequencing, and complementation of

Escherichia coli

strains lacking biotin synthase.

Arch. Biochem. Biophys.

309 (1994) 29–35. [PMID:

8117110

]

3. Trainor, D.A., Parry, R.J. and Gitterman, A. Biotin biosynthesis. 2. Stereochemistry of sulfur

introduction at C-4 of dethiobiotin.

J. Am. Chem. Soc.

102 (1980) 1467–1468.

4. Lotierzo, M., Tse Sum Bui, B., Florentin, D., Escalettes, F. and Marquet, A. Biotin synthase

mechanism: an overview.

Biochem. Soc. Trans.

33 (2005) 820–823. [PMID:

16042606

]

5. Berkovitch, F., Nicolet, Y., Wan, J.T., Jarrett, J.T. and Drennan, C.L. Crystal structure of biotin

synthase, an

-adenosylmethionine-dependent radical enzyme.

Science

303 (2004) 76–79.

[PMID:

14704425

]

6. Ugulava, N.B., Gibney, B.R. and Jarrett, J.T. Biotin synthase contains two distinct iron-sulfur

cluster binding sites: chemical and spectroelectrochemical analysis of iron-sulfur cluster
interconversions.

Biochemistry

40 (2001) 8343–8351. [PMID:

11444981

]

[EC 2.8.1.6 created 1999, modified 2006]

EC 2.8.1.8

Common name: lipoyl synthase

Reaction: protein 6-

-(octanoyl)lysine + 2 sulfur + 2

-adenosyl-

-methionine = protein 6-

-(lipoyl)lysine + 2

-methionine + 2 5′-deoxyadenosine

Other name(s): LS; LipA; lipoate synthase

Systematic name: protein 6-

-(octanoyl)lysine:sulfur sulfurtransferase

Comments: This enzyme is a member of the 'AdoMet radical' (radical SAM) family, all members of which

produce the 5′-deoxyadenosin-5′-yl radical and methionine from AdoMet [i.e.

adenosylmethionine, or

-(5′-deoxyadenosin-5′-yl)methionine], by the addition of an electron from

an iron-sulfur centre. The radical is converted into 5′-deoxyadenosine when it abstracts a hydrogen
atom from C-6 and C-8, leaving reactive radicals at these positions so that they can add sulfur, with
inversion of configuration [4]. This enzyme catalyses the final step in the de-novo biosynthesis of
the lipoyl cofactor, with the other enzyme involved being

EC 2.3.1.181

, lipoyl(octanoyl) transferase.

Lipoylation is essential for the function of several key enzymes involved in oxidative metabolism, as
it converts apoprotein into the biologically active holoprotein. Examples of such lipoylated proteins
include pyruvate dehydrogenase (E

domain), 2-oxoglutarate dehydrogenase (E

domain), the

branched-chain

2-oxoacid dehydrogenases

and the

glycine cleavage system

(H protein) [2,5]. An

alternative lipoylation pathway involves

EC 2.7.7.63

, lipoate—protein ligase, which can lipoylate

apoproteins using exogenous lipoic acid (or its analogues) [7].

References: 1. Cicchillo, R.M. and Booker, S.J. Mechanistic investigations of lipoic acid biosynthesis in

Escherichia coli

: both sulfur atoms in lipoic acid are contributed by the same lipoyl synthase

polypeptide.

J. Am. Chem. Soc.

127 (2005) 2860–2861. [PMID:

15740115

]

2. Vanden Boom, T.J., Reed, K.E. and Cronan, J.E., Jr. Lipoic acid metabolism in

Escherichia coli

isolation of null mutants defective in lipoic acid biosynthesis, molecular cloning and
characterization of the

E. coli

lip

locus, and identification of the lipoylated protein of the glycine

cleavage system.

J. Bacteriol.

173 (1991) 6411–6420. [PMID:

1655709

]

3. Zhao, X., Miller, J.R., Jiang, Y., Marletta, M.A. and Cronan, J.E. Assembly of the covalent linkage

between lipoic acid and its cognate enzymes.

Chem. Biol.

10 (2003) 1293–1302. [PMID:

14700636

]

4. Cicchillo, R.M., Iwig, D.F., Jones, A.D., Nesbitt, N.M., Baleanu-Gogonea, C., Souder, M.G., Tu,

L. and Booker, S.J. Lipoyl synthase requires two equivalents of

-adenosyl-

-methionine to

synthesize one equivalent of lipoic acid.

Biochemistry

43 (2004) 6378–6386. [PMID:

15157071

]

5. Jordan, S.W. and Cronan, J.E., Jr. A new metabolic link. The acyl carrier protein of lipid

synthesis donates lipoic acid to the pyruvate dehydrogenase complex in

Escherichia coli

and

mitochondria.

J. Biol. Chem.

272 (1997) 17903–17906. [PMID:

9218413

]

6. Miller, J.R., Busby, R.W., Jordan, S.W., Cheek, J., Henshaw, T.F., Ashley, G.W., Broderick, J.B.,

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Cronan, J.E., Jr. and Marletta, M.A.

Escherichia coli

LipA is a lipoyl synthase: in vitro

biosynthesis of lipoylated pyruvate dehydrogenase complex from octanoyl-acyl carrier protein.

Biochemistry

39 (2000) 15166–15178. [PMID:

11106496

]

7. Perham, R.N. Swinging arms and swinging domains in multifunctional enzymes: catalytic

machines for multistep reactions.

Annu. Rev. Biochem.

69 (2000) 961–1004. [PMID:

10966480

]

[EC 2.8.1.8 created 2006]

EC 3.1.3.76

Common name: lipid-phosphate phosphatase

Reaction: (9

,10

)-10-hydroxy-9-(phosphonooxy)octadecanoate + H

O = (9

,10

)-9,10-

dihydroxyoctadecanoate + phosphate

Other name(s): hydroxy fatty acid phosphatase; dihydroxy fatty acid phosphatase; hydroxy lipid phosphatase; sEH

(ambiguous); soluble epoxide hydrolase (ambiguous)

Systematic name: (9

,10

)-10-hydroxy-9-(phosphonooxy)octadecanoate phosphohydrolase

Comments: Requires Mg

for maximal activity. The enzyme from mammals is a bifunctional enzyme: the N-

terminal domain exhibits lipid-phosphate-phosphatase activity and the C-terminal domain has the
activity of

EC 3.3.2.10

, soluble epoxide hydrolase (sEH) [1]. The best substrates for this enzyme

are 10-hydroxy-9-(phosphonooxy)octadecanoates, with the

threo

- form being a better substrate

than the

erythro

- form [1]. The phosphatase activity is not found in plant sEH or in

EC 3.3.2.9

microsomal epoxide hydrolase, from mammals [1].

References: 1. Newman, J.W., Morisseau, C., Harris, T.R. and Hammock, B.D. The soluble epoxide hydrolase

encoded by EPXH

is a bifunctional enzyme with novel lipid phosphate phosphatase activity.

Proc. Natl. Acad. Sci. USA

100 (2003) 1558–1563. [PMID:

12574510

]

2. Cronin, A., Mowbray, S., Dürk, H., Homburg, S., Fleming, I., Fisslthaler, B., Oesch, F. and Arand,

M. The N-terminal domain of mammalian soluble epoxide hydrolase is a phosphatase.

Proc.

Natl. Acad. Sci. USA

100 (2003) 1552–1557. [PMID:

12574508

]

3. Morisseau, C. and Hammock, B.D. Epoxide hydrolases: mechanisms, inhibitor designs, and

biological roles.

Annu. Rev. Pharmacol. Toxicol.

45 (2005) 311–333. [PMID:

15822179

]

4. Tran, K.L., Aronov, P.A., Tanaka, H., Newman, J.W., Hammock, B.D. and Morisseau, C. Lipid

sulfates and sulfonates are allosteric competitive inhibitors of the N-terminal phosphatase activity
of the mammalian soluble epoxide hydrolase.

Biochemistry

44 (2005) 12179–12187. [PMID:

16142916

]

5. Newman, J.W., Morisseau, C. and Hammock, B.D. Epoxide hydrolases: their roles and

interactions with lipid metabolism.

Prog. Lipid Res.

44 (2005) 1–51. [PMID:

15748653

]

6. Srivastava, P.K., Sharma, V.K., Kalonia, D.S. and Grant, D.F. Polymorphisms in human soluble

epoxide hydrolase: effects on enzyme activity, enzyme stability, and quaternary structure.

Arch.

Biochem. Biophys.

427 (2004) 164–169. [PMID:

15196990

]

7. Gomez, G.A., Morisseau, C., Hammock, B.D. and Christianson, D.W. Structure of human

epoxide hydrolase reveals mechanistic inferences on bifunctional catalysis in epoxide and
phosphate ester hydrolysis.

Biochemistry

43 (2004) 4716–4723. [PMID:

15096040

]

[EC 3.1.3.76 created 2006]

EC 3.1.13.5

Common name: ribonuclease D

Reaction: Exonucleolytic cleavage that removes extra residues from the 3′-terminus of tRNA to produce 5′-

mononucleotides

Other name(s): RNase D

Comments: Requires divalent cations for activity (Mg

, Mn

or Co

). Alteration of the 3′-terminal base has

no effect on the rate of hydrolysis whereas modification of the 3′-terminal sugar has a major effect.
tRNA terminating with a 3′-phosphate is completely inactive [3]. This enzyme can convert a tRNA
precursor into a mature tRNA [2].

References: 1. Ghosh, R.K. and Deutscher, M.P. Identification of an

Escherichia coli

nuclease acting on

structurally altered transfer RNA molecules.

J. Biol. Chem.

253 (1978) 997–1000. [PMID:

342522

]

2. Cudny, H., Zaniewski, R. and Deutscher, M.P.

Escherichia coli

RNase D. Purification and

structural characterization of a putative processing nuclease.

J. Biol. Chem.

256 (1981) 5627–

5632. [PMID:

6263885

]

3. Cudny, H., Zaniewski, R. and Deutscher, M.P.

Escherichia coli

RNase D. Catalytic properties

and substrate specificity.

J. Biol. Chem.

256 (1981) 5633–5637. [PMID:

6263886

]

4. Zhang, J.R. and Deutscher, M.P. Cloning, characterization, and effects of overexpression of the

06/27/2006 05:11 PM

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Escherichia coli

rnd

gene encoding RNase D.

J. Bacteriol.

170 (1988) 522–527. [PMID:

2828310

]

[EC 3.1.13.5 created 2006]

*EC 3.1.26.3

Common name: ribonuclease III

Reaction: Endonucleolytic cleavage to a 5′-phosphomonoester

Other name(s): RNase III; ribonuclease 3

Comments: This is an endoribonuclease that cleaves double-stranded RNA molecules [4]. The cleavage can be

either a single-stranded nick or double-stranded break in the RNA, depending in part upon the
degree of base-pairing in the region of the cleavage site [5]. Specificity is conferred by negative
determinants, i.e., the presence of certain Watson-Crick base-pairs at specific positions that
strongly inhibit cleavage [6]. RNase III is involved in both rRNA processing and mRNA processing
and decay.

Links to other databases:

BRENDA

ERGO

EXPASY

IUBMB

KEGG

PDB

, CAS registry number: 78413-14-6

References: 1. Crouch, R.J. Ribonuclease 3 does not degrade deoxyribonucleic acid-ribonucleic acid hybrids.

Biol. Chem.

249 (1974) 1314–1316. [PMID:

4592261

]

2. Rech, J., Cathala, G. and Jeanteur, P. Isolation and characterization of a ribonuclease activity

specific for double-stranded RNA (RNase D) from Krebs II ascites cells.

J. Biol. Chem.

255

(1980) 6700–6706. [PMID:

6248530

]

3. Robertson, H.D., Webster, R.E. and Zinder, N.D. Purification and properties of ribonuclease III

from

Escherichia coli

J. Biol. Chem.

243 (1968) 82–91. [PMID:

4865702

]

4. Grunberg-Manago, M. Messenger RNA stability and its role in control of gene expression in

bacteria and phages.

Annu. Rev. Genet.

33 (1999) 193–227. [PMID:

10690408

]

5. Court, D. RNA processing and degradation by RNase III in control of mRNA stability. In:

Belasco, J.G. and Brawerman, G. (Eds),

Control of Messenger RNA Stability

, Academic Press,

New York, 1993, pp. 71–116.

6. Zhang, K. and Nicholson, A.W. Regulation of ribonuclease III processing by double-helical

sequence antideterminants.

Proc. Natl. Acad. Sci. USA

94 (1997) 13437–13441. [PMID:

9391043

]

[EC 3.1.26.3 created 1978, modified 2006]

*EC 3.2.1.81

Common name: β-agarase

Reaction: Hydrolysis of 1,4-β-

-galactosidic linkages in agarose, giving the tetramer as the predominant

product

Glossary:

agarose

= a polysaccharide

In the field of oligosaccharides derived from agarose, carrageenans, etc., in which alternate
residues are 3,6-anhydro sugars, the prefix 'neo' designates an oligosaccharide whose non-
reducing end is the anhydro sugar, and the absence of this prefix means that it is not. For example:
neoagarobiose = 3,6-anhydro-α-

-galactopyranosyl-(1→3)-

-galactose agarobiose = β-

galactopyranosyl-(1→4)-3,6-anhydro-

-galactose

Other name(s): agarase (ambiguous); AgaA; AgaB; endo-β-agarase; agarose 3-glycanohydrolase (incorrect)

Systematic name: agarose 4-glycanohydrolase

Comments: Also acts on porphyran, but more slowly [1]. This enzyme cleaves the β-(1→4) linkages of agarose

in a random manner with retention of the anomeric-bond configuration, producing β-anomers that
give rise progressively to α-anomers when mutarotation takes place [6]. The end products of
hydrolysis are neoagarotetraose and neoagarohexaose in the case of AgaA from the marine
bacterium

Zobellia galactanivorans

, and neoagarotetraose and neoagarobiose in the case of AgaB

[6].

Links to other databases:

BRENDA

ERGO

EXPASY

IUBMB

KEGG

PDB

, CAS registry number: 37288-57-6

References: 1. Duckworth, M. and Turvey, J.R. The action of a bacterial agarase on agarose, porphyran and

alkali-treated porphyran.

Biochem. J.

113 (1969) 687–692. [PMID:

5386190

]

2. Allouch, J., Jam, M., Helbert, W., Barbeyron, T., Kloareg, B., Henrissat, B. and Czjzek, M. The

three-dimensional structures of two β-agarases.

J. Biol. Chem.

278 (2003) 47171–47180. [PMID:

12970344

]

3. Ohta, Y., Nogi, Y., Miyazaki, M., Li, Z., Hatada, Y., Ito, S. and Horikoshi, K. Enzymatic properties

and nucleotide and amino acid sequences of a thermostable β-agarase from the novel marine
isolate, JAMB-A94.

Biosci. Biotechnol. Biochem.

68 (2004) 1073–1081. [PMID:

15170112

]

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The Enzyme Database: New Enzymes

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4. Ohta, Y., Hatada, Y., Nogi, Y., Miyazaki, M., Li, Z., Akita, M., Hidaka, Y., Goda, S., Ito, S. and

Horikoshi, K. Enzymatic properties and nucleotide and amino acid sequences of a thermostable
β-agarase from a novel species of deep-sea

Microbulbifer

Appl. Microbiol. Biotechnol.

64 (2004)

505–514. [PMID:

15088129

]

5. Sugano, Y., Terada, I., Arita, M., Noma, M. and Matsumoto, T. Purification and characterization

of a new agarase from a marine bacterium,

Vibrio

sp. strain JT0107.

Appl. Environ. Microbiol.

(1993) 1549–1554. [PMID:

8517750

]

6. Jam, M., Flament, D., Allouch, J., Potin, P., Thion, L., Kloareg, B., Czjzek, M., Helbert, W.,

Michel, G. and Barbeyron, T. The endo-β-agarases AgaA and AgaB from the marine bacterium

Zobellia galactanivorans

: two paralogue enzymes with different molecular organizations and

catalytic behaviours.

Biochem. J.

385 (2005) 703–713. [PMID:

15456406

]

[EC 3.2.1.81 created 1972, modified 2006]

*EC 3.2.1.83

Common name: κ-carrageenase

Reaction: Endohydrolysis of 1,4-β-

-linkages between

-galactose 4-sulfate and 3,6-anhydro-

-galactose in

κ-carrageenans
For diagram of reaction,

click here

Glossary: In the field of oligosaccharides derived from agarose, carrageenans, etc., in which alternate

residues are 3,6-anhydro sugars, the prefix 'neo' designates an oligosaccharide whose non-
reducing end is the anhydro sugar, and the absence of this prefix means that it is not.
For example:
ι-neocarrabiose = 3,6-anhydro-2-

-sulfo-α-

-galactopyranosyl-(1→3)-4-

-sulfo-

-galactose

ι-carrabiose = 4-

-sulfo- β-

-galactopyranosyl-(1→4)-3,6-anhydro-2-

-sulfo-

-galactose

Other name(s): κ-carrageenan 4-β-

-glycanohydrolase

Systematic name: κ-carrageenan 4-β-

-glycanohydrolase (configuration-retaining)

Comments: The main products of hydrolysis are neocarrabiose-sulfate and neocarratetraose-sulfate [5]. Unlike

EC 3.2.1.157

(ι-carrageenase), but similar to

EC 3.2.1.81

(β-agarase), this enzyme proceeds with

retention of the anomeric configuration.

Links to other databases:

BRENDA

ERGO

EXPASY

IUBMB

KEGG

PDB

, CAS registry number: 37288-59-8

References: 1. Weigl, J. and Yashe, W. The enzymic hydrolysis of carrageenan by

Pseudomonas

carrageenovora

: purification of a κ-carrageenase.

Can. J. Microbiol.

12 (1966) 939–947. [PMID:

5972647

]

2. Potin, P., Sanseau, A., Le Gall, Y., Rochas, C. and Kloareg, B. Purification and characterization

of a new κ-carrageenase from a marine

Cytophaga

-like bacterium.

Eur. J. Biochem.

201 (1991)

241–247. [PMID:

1915370

]

3. Potin, P., Richard, C., Barbeyron, T., Henrissat, B., Gey, C., Petillot, Y., Forest, E., Dideberg, O.,

Rochas, C. and Kloareg, B. Processing and hydrolytic mechanism of the

cgkA

-encoded κ-

carrageenase of

Alteromonas carrageenovora

Eur. J. Biochem.

228 (1995) 971–975. [PMID:

7737202

]

4. Michel, G., Barbeyron, T., Flament, D., Vernet, T., Kloareg, B. and Dideberg, O. Expression,

purification, crystallization and preliminary x-ray analysis of the κ-carrageenase from

Pseudoalteromonas carrageenovora

Acta Crystallogr. D Biol. Crystallogr.

55 (1999) 918–920.

[PMID:

10089334

]

5. Michel, G., Chantalat, L., Duee, E., Barbeyron, T., Henrissat, B., Kloareg, B. and Dideberg, O.

The κ-carrageenase of

P. carrageenovora

features a tunnel-shaped active site: a novel insight in

the evolution of Clan-B glycoside hydrolases.

Structure

9 (2001) 513–525. [PMID:

11435116

]

[EC 3.2.1.83 created 1972, modified 2006]

EC 3.2.1.155

Common name: xyloglucan-specific exo-β-1,4-glucanase

Reaction: xyloglucan + H

O = xyloglucan oligosaccharides (exohydrolysis of 1,4-β-

-glucosidic linkages in

xyloglucan)

Other name(s): Cel74A

Systematic name: [(1→6)-α-

-xylo]-(1→4)-β-

-glucan exo-glucohydrolase

Comments: The enzyme from

Chrysosporium lucknowense

is an endoglucanase, i.e. acquires the specificity of

EC 3.2.1.151

, xyloglucan-specific endo-β-1,4-glucanase, when it acts on linear substrates without

bulky substituents on the polymeric backbone (e.g. carboxymethylcellulose). However, it switches
to an exoglucanase mode of action when bulky side chains are present (as in the case of

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xyloglucan). The enzyme can also act on barley β-glucan, but more slowly.

Links to other databases:

BRENDA

ERGO

EXPASY

IUBMB

KEGG

References: 1. Grishutin, S.G., Gusakov, A.V., Markov, A.V., Ustinov, B.B., Semenova, M.V. and Sinitsyn, A.P.

Specific xyloglucanases as a new class of polysaccharide-degrading enzymes.

Biochim.

Biophys. Acta

1674 (2004) 268–281. [PMID:

15541296

]

[EC 3.2.1.155 created 2005, withdrawn at public-review stage, modified and reinstated 2006]

EC 3.2.1.157

Common name: ι-carrageenase

Reaction: Endohydrolysis of 1,4-β-

-linkages between

-galactose 4-sulfate and 3,6-anhydro-

-galactose-2-

sulfate in ι-carrageenans

For diagram of reaction,

click here

Glossary: In the field of oligosaccharides derived from agarose, carrageenans, etc., in which alternate

-sulfo-α-

-galactopyranosyl-(1→3)-4-

-sulfo-

-galactose

ι-carrabiose = 4-

-sulfo-β-

-galactopyranosyl-(1→4)-3,6-anhydro-2-

-sulfo-

-galactose

Systematic name: ι-carrageenan 4-β-

-glycanohydrolase (configuration-inverting)

Comments: The main products of hydrolysis are ι-neocarratetraose sulfate and ι-neocarrahexaose sulfate. ι-

Neocarraoctaose is the shortest substrate oligomer that can be cleaved. Unlike

EC 3.2.1.81

, β-

agarase and

EC 3.2.1.83

, κ-carrageenase, this enzyme proceeds with inversion of the anomeric

configuration. ι-Carrageenan differs from κ-carrageenan by possessing a sulfo group on

-2 of the

3,6-anhydro-

-galactose residues, in addition to that present in the κ-compound on

-4 of the

galactose residues.

References: 1. Barbeyron, T., Michel, G., Potin, P., Henrissat, B. and Kloareg, B. ι-Carrageenases constitute a

novel family of glycoside hydrolases, unrelated to that of κ-carrageenases.

J. Biol. Chem.

275

(2000) 35499–35505. [PMID:

10934194

]

2. Michel, G., Chantalat, L., Fanchon, E., Henrissat, B., Kloareg, B. and Dideberg, O. The ι-

carrageenase of

Alteromonas fortis

. A β-helix fold-containing enzyme for the degradation of a

highly polyanionic polysaccharide.

J. Biol. Chem.

276 (2001) 40202–40209. [PMID:

11493601

]

3. Michel, G., Helbert, W., Kahn, R., Dideberg, O. and Kloareg, B. The structural bases of the

processive degradation of ι-carrageenan, a main cell wall polysaccharide of red algae.

J. Mol.

Biol.

334 (2003) 421–433. [PMID:

14623184

]

[EC 3.2.1.157 created 2006]

EC 3.2.1.158

Common name: α-agarase

Reaction: Endohydrolysis of 1,3-α-

-galactosidic linkages in agarose, yielding agarotetraose as the major

product

Glossary:

agarose

= a polysaccharide

-galactopyranosyl-(1→3)-

-galactose

agarobiose = β-

-galactopyranosyl-(1→4)-3,6-anhydro-

-galactose

Other name(s): agarase (ambiguous); agaraseA33

Systematic name: agarose 3-glycanohydrolase

Comments: Requires Ca

. The enzyme from

Thalassomonas

sp. can use agarose, agarohexaose and

neoagarohexaose as substrate. The products of agarohexaose hydrolysis are dimers and
tetramers, with agarotetraose being the predominant product, whereas hydrolysis of
neoagarohexaose gives rise to two types of trimer. While the enzyme can also hydrolyse the highly
sulfated agarose porphyran very efficiently, it cannot hydrolyse the related compounds κ-
carrageenan (see

EC 3.2.1.83

) and ι-carrageenan (see

EC 3.2.1.157

) [2]. See also

EC 3.2.1.81

, β-

agarase.

References: 1. Potin, P., Richard, C., Rochas, C. and Kloareg, B. Purification and characterization of the α-

agarase from

Alteromonas agarlyticus

(Cataldi) comb. nov., strain GJ1B.

Eur. J. Biochem.

214

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(1993) 599–607. [PMID:

8513809

]

2. Ohta, Y., Hatada, Y., Miyazaki, M., Nogi, Y., Ito, S. and Horikoshi, K. Purification and

characterization of a novel α-agarase from a

Thalassomonas

sp.

Curr. Microbiol.

50 (2005) 212–

216. [PMID:

15902469

]

[EC 3.2.1.158 created 2006]

EC 3.2.1.159

Common name: α-neoagaro-oligosaccharide hydrolase

Reaction: Hydrolysis of the 1,3-α-

-galactosidic linkages of neoagaro-oligosaccharides that are smaller than a

hexamer, yielding 3,6-anhydro-

-galactose and

-galactose

Glossary: In the field of oligosaccharides derived from agarose, carrageenans, etc., in which alternate

-galactopyranosyl-(1→3)-

-galactose

agarobiose = β-

-galactopyranosyl-(1→4)-3,6-anhydro-

-galactose

Other name(s): α-neoagarooligosaccharide hydrolase; α-NAOS hydrolase

Systematic name: α-neoagaro-oligosaccharide 3-glycohydrolase

Comments: When neoagarohexaose is used as a substrate, the oligosaccharide is cleaved at the non-reducing

end to produce 3,6-anhydro-

-galactose and agaropentaose, which is further hydrolysed to

agarobiose and agarotriose. With neoagarotetraose as substrate, the products are predominantly
agarotriose and 3,6-anhydro-

-galactose. In

Vibrio

sp. the actions of

EC 3.2.1.81

, β-agarase and

EC 3.2.1.159 can be used to degrade agarose to 3,6-anhydro-

-galactose and

-galactose.

References: 1. Sugano, Y., Kodama, H., Terada, I., Yamazaki, Y. and Noma, M. Purification and

characterization of a novel enzyme, α-neoagarooligosaccharide hydrolase (α-NAOS hydrolase),
from a marine bacterium,

Vibrio

sp. strain JT0107.

J. Bacteriol.

176 (1994) 6812–6818. [PMID:

7961439

]

[EC 3.2.1.159 created 2006]

EC 3.2.1.161

Common name: β-apiosyl-β-glucosidase

Reaction: 7-[β-

-apiofuranosyl-(1→6)-β-

-glucopyranosyloxy]isoflavonoid + H

O = a 7-hydroxyisoflavonoid +

β-

-apiofuranosyl-(1→6)-

-glucose

Other name(s): isoflavonoid-7-

-β[

-apiosyl-(1→6)-β-

-glucoside] disaccharidase; isoflavonoid 7-

-β-apiosyl-

glucoside β-glucosidase; furcatin hydrolase

Systematic name: 7-[β-

-apiofuranosyl-(1→6)-β-

-glucopyranosyloxy]isoflavonoid β-

-apiofuranosyl-(1→6)-

glucohydrolase

Comments: The enzyme from the tropical tree

Dalbergia nigrescens

Kurz belongs in glycosyl hydrolase family

1. The enzyme removes disaccharides from the natural substrates dalpatein 7-

-β-

apiofuranosyl-(1→6)-β-

-glucopyranoside and 7-hydroxy-2′,4′,5′,6-tetramethoxy-7-

-β-

apiofuranosyl-(1→6)-β-

-glucopyranoside (dalnigrein 7-

-β-

-apiofuranosyl-(1→6)-β-

glucopyranoside) although it can also remove a single glucose residue from isoflavonoid 7-

glucosides [2]. Daidzin and genistin are also substrates.

References: 1. Hosel, W. and Barz, W. β-Glucosidases from

Cicer arietinum

L. Purification and Properties of

isoflavone-7-

-glucoside-specific β-glucosidases.

Eur. J. Biochem.

57 (1975) 607–616. [PMID:

240725

]

2. Chuankhayan, P., Hua, Y., Svasti, J., Sakdarat, S., Sullivan, P.A. and Ketudat Cairns, J.R.

Purification of an isoflavonoid 7-

-β-apiosyl-glucoside β-glycosidase and its substrates from

Dalbergia nigrescens

Kurz.

Phytochemistry

66 (2005) 1880–1889. [PMID:

16098548

]

3. Ahn, Y.O., Mizutani, M., Saino, H. and Sakata, K. Furcatin hydrolase from

Viburnum furcatum

Blume is a novel disaccharide-specific acuminosidase in glycosyl hydrolase family 1.

J. Biol.

Chem.

279 (2004) 23405–23414. [PMID:

14976214

]

[EC 3.2.1.161 created 2006]

EC 3.3.2.3

Transferred entry: epoxide hydrolase. Now known to comprise two enzymes, microsomal epoxide hydrolase (

3.3.2.9

) and soluble epoxide hydrolase (

EC 3.3.2.10

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[EC 3.3.2.3 created 1978, modified 1999, deleted 2006]

*EC 3.3.2.6

Common name: leukotriene-A

hydrolase

Reaction: (7

,11

,14

)-(5

)-5,6-epoxyicosa-7,9,11,14-tetraenoate + H

O = (6

,10

,14

,12

)-5,12-dihydroxyicosa-6,8,10,14-tetraenoate

Glossary: leukotriene A

= (7

,11

,14

)-(5

)-5,6-epoxyicosa-7,9,11,14-tetraenoate

leukotriene B

= (6

,10

,14

)-(5

,12

)-5,12-dihydroxyicosa-6,8,10,14-tetraenoate

Other name(s): LTA

hydrolase; LTA4H; leukotriene A

hydrolase

Systematic name: (7

,11

,14

)-(5

)-5,6-epoxyicosa-7,9,11,14-tetraenoate hydrolase

Comments: This is a bifunctional zinc metalloprotease that displays both epoxide hydrolase and

aminopeptidase activities [4,6]. It preferentially cleaves tripeptides at an arginyl bond, with
dipeptides and tetrapeptides being poorer substrates [6] (see

EC 3.4.11.6

, aminopeptidase B). It

also converts leukotriene A

into leukotriene B

, unlike

EC 3.2.2.10

, soluble epoxide hydrolase,

which converts leukotriene A

into 5,6-dihydroxy-7,9,11,14-icosatetraenoic acid [3,4]. In

vertebrates, five epoxide-hydrolase enzymes have been identified to date: EC 3.3.2.6 (leukotriene
A

hydrolase),

EC 3.3.2.7

(hepoxilin-epoxide hydrolase),

EC 3.3.2.9

(microsomal epoxide

hydrolase),

EC 3.3.2.10

(soluble epoxide hydrolase) and

EC 3.3.2.11

(cholesterol-5,6-oxide

hydrolase) [3].

Links to other databases:

BRENDA

ERGO

EXPASY

IUBMB

KEGG

PDB

, CAS registry number: 90119-07-6

References: 1. Evans, J.F., Dupuis, P. and Ford-Hutchinson, A.W. Purification and characterisation of

leukotriene A

hydrolase from rat neutrophils.

Biochim. Biophys. Acta

840 (1985) 43–50. [PMID:

3995081

]

2. Minami, M., Ohno, S., Kawasaki, H., Rådmark, O., Samuelsson, B., Jörnvall, H., Shimizu, T.,

Seyama, Y. and Suzuki, K. Molecular cloning of a cDNA coding for human leukotriene A

hydrolase - complete primary structure of an enzyme involved in eicosanoid synthesis.

J. Biol.

Chem.

262 (1987) 13873–13876. [PMID:

3654641

]

3. Haeggström, J., Meijer, J. and Rådmark, O. Leukotriene A

. Enzymatic conversion into 5,6-

dihydroxy-7,9,11,14-eicosatetraenoic acid by mouse liver cytosolic epoxide hydrolase.

J. Biol.

Chem.

261 (1986) 6332–6337. [PMID:

3009453

]

4. Newman, J.W., Morisseau, C. and Hammock, B.D. Epoxide hydrolases: their roles and

interactions with lipid metabolism.

Prog. Lipid Res.

44 (2005) 1–51. [PMID:

15748653

]

5. Fretland, A.J. and Omiecinski, C.J. Epoxide hydrolases: biochemistry and molecular biology.

Chem. Biol. Interact.

129 (2000) 41–59. [PMID:

11154734

]

6. Orning, L., Gierse, J.K. and Fitzpatrick, F.A. The bifunctional enzyme leukotriene-A

hydrolase is

an arginine aminopeptidase of high efficiency and specificity.

J. Biol. Chem.

269 (1994) 11269–

11267. [PMID:

8157657

]

7. Ohishi, N., Izumi, T., Minami, M., Kitamura, S., Seyama, Y., Ohkawa, S., Terao, S., Yotsumoto,

H., Takaku, F. and Shimizu, T. Leukotriene A

hydrolase in the human lung. Inactivation of the

enzyme with leukotriene A

isomers.

J. Biol. Chem.

262 (1987) 10200–10205. [PMID:

3038871

]

[EC 3.3.2.6 created 1989, modified 2006]

*EC 3.3.2.7

Common name: hepoxilin-epoxide hydrolase

Reaction: (5

,14

)-(8ξ,11

,12

)-11,12-epoxy-8-hydroxyicosa-5,9,14-trienoate + H

O = (5

,14

(8ξ,11ξ,12

)-8,11,12-trihydroxyicosa-5,9,14-trienoate

Glossary: hepoxilin A

= (5

,14

)-(8ξ,11

,12

)-11,12-epoxy-8-hydroxyicosa-5,9,14-trienoate

trioxilin A

= (5

,14

)-(8ξ,11ξ,12

)-8,11,12-trihydroxyicosa-5,9,14-trienoate

Other name(s): hepoxilin epoxide hydrolase; hepoxylin hydrolase; hepoxilin A

hydrolase

Systematic name: (5

,14

)-(8ξ,11

,12

)-11,12-epoxy-8-hydroxyicosa-5,9,14-trienoate hydrolase

Comments: Converts hepoxilin A

into trioxilin A

. Highly specific for the substrate, having only slight activity

with other epoxides such as leukotriene A

and styrene oxide [2]. Hepoxilin A

is an hydroxy-

epoxide derivative of arachidonic acid that is formed via the 12-lipoxygenase pathway [2]. It is
probable that this enzyme plays a modulatory role in inflammation, vascular physiology, systemic
glucose metabolism and neurological function [4]. In vertebrates, five epoxide-hydrolase enzymes
have been identified to date:

EC 3.3.2.6

(leukotriene-A

hydrolase), EC 3.3.2.7 (hepoxilin-epoxide

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hydrolase),

EC 3.3.2.9

(microsomal epoxide hydrolase),

EC 3.3.2.10

(soluble epoxide hydrolase)

and

EC 3.3.2.11

(cholesterol 5,6-oxide hydrolase) [3].

Links to other databases:

BRENDA

ERGO

EXPASY

IUBMB

KEGG

, CAS registry number: 122096-98-4

References: 1. Pace-Asciak, C.R. Formation and metabolism of hepoxilin A

by the rat brain.

Biochem.

Biophys. Res. Commun.

151 (1988) 493–498. [PMID:

3348791

]

2. Pace-Asciak, C.R. and Lee, W.-S. Purification of hepoxilin epoxide hydrolase from rat liver.

Biol. Chem.

264 (1989) 9310–9313. [PMID:

2722835

]

3. Fretland, A.J. and Omiecinski, C.J. Epoxide hydrolases: biochemistry and molecular biology.

Chem. Biol. Interact.

129 (2000) 41–59. [PMID:

11154734

]

4. Newman, J.W., Morisseau, C. and Hammock, B.D. Epoxide hydrolases: their roles and

interactions with lipid metabolism.

Prog. Lipid Res.

44 (2005) 1–51. [PMID:

15748653

]

[EC 3.3.2.7 created 1992, modified 2006]

EC 3.3.2.9

Common name: microsomal epoxide hydrolase

Reaction:

cis

-stilbene oxide + H

O = (+)-(1

)-1,2-diphenylethane-1,2-diol

Other name(s): epoxide hydratase (ambiguous); microsomal epoxide hydratase (ambiguous); epoxide hydrase;

microsomal epoxide hydrase; arene-oxide hydratase (ambiguous); benzo[

]pyrene-4,5-oxide

hydratase; benzo(a)pyrene-4,5-epoxide hydratase; aryl epoxide hydrase (ambiguous);

cis

-epoxide

hydrolase; mEH

Systematic name:

cis

-stilbene-oxide hydrolase

Comments: This is a key hepatic enzyme that is involved in the metabolism of numerous xenobiotics, such as

1,3-butadiene oxide, styrene oxide and the polycyclic aromatic hydrocarbon benzo[

]pyrene 4,5-

oxide [5—7]. In a series of oxiranes with a lipophilic substituent of sufficient size (styrene oxides),
monosubstituted as well as 1,1- and

cis

-1,2-disubstituted oxiranes serve as substrates or inhibitors

of the enzyme. However,

trans

-1,2-disubstituted, tri-and tetra-substituted oxiranes are not

substrates [9]. The reaction involves the formation of an hydroxyalkyl—enzyme intermediate [10].
In vertebrates, five epoxide-hydrolase enzymes have been identified to date:

EC 3.3.2.6

(leukotriene-A

hydrolase),

EC 3.3.2.7

(hepoxilin-epoxide hydrolase), EC 3.3.2.9 (microsomal

epoxide hydrolase),

EC 3.3.2.10

(soluble epoxide hydrolase) and

EC 3.3.2.11

(cholesterol-5,6-

oxide hydrolase) [7].

References: 1. Jakoby, W.B. and Fjellstedt, T.A. Epoxidases. In: Boyer, P.D. (Ed.),

The Enzymes

, 3rd edn,

vol. 7, Academic Press, New York, 1972, pp. 199–212.

2. Lu, A.Y., Ryan, D., Jerina, D.M., Daly, J.W. and Levin, W. Liver microsomal expoxide hydrase.

Solubilization, purification, and characterization.

J. Biol. Chem.

250 (1975) 8283–8288. [PMID:

240858

]

3. Oesch, F. Purification and specificity of a human microsomal epoxide hydratase.

Biochem. J.

139 (1974) 77–88. [PMID:

4463951

]

4. Oesch, F. and Daly, J. Solubilization, purification, and properties of a hepatic epoxide hydrase.

Biochim. Biophys. Acta

227 (1971) 692–697. [PMID:

4998715

]

5. Bellucci, G., Chiappe, C. and Ingrosso, G. Kinetics and stereochemistry of the microsomal

epoxide hydrolase-catalyzed hydrolysis of

cis

-stilbene oxides.

Chirality

6 (1994) 577–582.

[PMID:

7986671

]

6. Morisseau, C. and Hammock, B.D. Epoxide hydrolases: mechanisms, inhibitor designs, and

biological roles.

Annu. Rev. Pharmacol. Toxicol.

45 (2005) 311–333. [PMID:

15822179

]

7. Fretland, A.J. and Omiecinski, C.J. Epoxide hydrolases: biochemistry and molecular biology.

Chem. Biol. Interact.

129 (2000) 41–59. [PMID:

11154734

]

8. Oesch, F. Mammalian epoxide hydrases: inducible enzymes catalysing the inactivation of

carcinogenic and cytotoxic metabolites derived from aromatic and olefinic compounds.

Xenobiotica

3 (1973) 305–340. [PMID:

4584115

]

9. Lacourciere, G.M. and Armstrong, R.N. Microsomal and soluble epoxide hydrolases are

members of the same family of C-X bond hydrolase enzymes.

Chem. Res. Toxicol.

7 (1994)

121–124. [PMID:

8199297

]

10. Newman, J.W., Morisseau, C. and Hammock, B.D. Epoxide hydrolases: their roles and

interactions with lipid metabolism.

Prog. Lipid Res.

44 (2005) 1–51. [PMID:

15748653

]

[EC 3.3.2.9 created 2006 (EC 3.3.2.3 part-incorporated 2006)]

EC 3.3.2.10

Common name: soluble epoxide hydrolase

Reaction: an epoxide + H

O = a glycol

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Other name(s): epoxide hydrase (ambiguous); epoxide hydratase (ambiguous); arene-oxide hydratase

(ambiguous); aryl epoxide hydrase (ambiguous);

trans

-stilbene oxide hydrolase; sEH; cytosolic

epoxide hydrolase

Systematic name: epoxide hydrolase

Comments: Catalyses the hydrolysis of

trans

-substituted epoxides, such as

trans

-stilbene oxide, as well as

various aliphatic epoxides derived from fatty-acid metabolism [7]. It is involved in the metabolism of
arachidonic epoxides (epoxyicosatrienoic acids; EETs) and linoleic acid epoxides. The EETs, which
are endogenous chemical mediators, act at the vascular, renal and cardiac levels to regulate blood
pressure [4,5]. The enzyme from mammals is a bifunctional enzyme: the C-terminal domain exhibits
epoxide-hydrolase activity and the N-terminal domain has the activity of

EC 3.1.3.76

, lipid-

phosphate phosphatase [1,2]. Like

EC 3.3.2.9

, microsomal epoxide hydrolase, it is probable that

the reaction involves the formation of an hydroxyalkyl—enzyme intermediate [4,6]. The enzyme can
also use leukotriene A

, the substrate of

EC 3.3.2.6

, leukotriene-A

hydrolase, but it forms 5,6-

dihydroxy-7,9,11,14-icosatetraenoic acid rather than leukotriene B

as the product [9,10]. In

vertebrates, five epoxide-hydrolase enzymes have been identified to date:

EC 3.3.2.6

(leukotriene-

hydrolase),

EC 3.3.2.7

(hepoxilin-epoxide hydrolase),

EC 3.3.2.9

(microsomal epoxide

hydrolase), EC 3.3.2.10 (soluble epoxide hydrolase) and

EC 3.3.2.11

(cholesterol 5,6-oxide

hydrolase) [7].

References: 1. Newman, J.W., Morisseau, C., Harris, T.R. and Hammock, B.D. The soluble epoxide hydrolase

encoded by EPXH

is a bifunctional enzyme with novel lipid phosphate phosphatase activity.

Proc. Natl. Acad. Sci. USA

100 (2003) 1558–1563. [PMID:

12574510

]

2. Cronin, A., Mowbray, S., Dürk, H., Homburg, S., Fleming, I., Fisslthaler, B., Oesch, F. and

Arand, M. The N-terminal domain of mammalian soluble epoxide hydrolase is a phosphatase.

Proc. Natl. Acad. Sci. USA

100 (2003) 1552–1557. [PMID:

12574508

]

3. Oesch, F. Mammalian epoxide hydrases: inducible enzymes catalysing the inactivation of

carcinogenic and cytotoxic metabolites derived from aromatic and olefinic compounds.

Xenobiotica

3 (1973) 305–340. [PMID:

4584115

]

4. Morisseau, C. and Hammock, B.D. Epoxide hydrolases: mechanisms, inhibitor designs, and

biological roles.

Annu. Rev. Pharmacol. Toxicol.

45 (2005) 311–333. [PMID:

15822179

]

5. Yu, Z., Xu, F., Huse, L.M., Morisseau, C., Draper, A.J., Newman, J.W., Parker, C., Graham, L.,

Engler, M.M., Hammock, B.D., Zeldin, D.C. and Kroetz, D.L. Soluble epoxide hydrolase
regulates hydrolysis of vasoactive epoxyeicosatrienoic acids.

Circ. Res.

87 (2000) 992–998.

[PMID:

11090543

]

6. Lacourciere, G.M. and Armstrong, R.N. The catalytic mechanism of microsomal epoxide

hydrolase involves an ester intermediate.

J. Am. Chem. Soc.

115 (1993) 10466–10456.

7. Fretland, A.J. and Omiecinski, C.J. Epoxide hydrolases: biochemistry and molecular biology.

Chem. Biol. Interact.

129 (2000) 41–59. [PMID:

11154734

]

8. Zeldin, D.C., Wei, S., Falck, J.R., Hammock, B.D., Snapper, J.R. and Capdevila, J.H.

Metabolism of epoxyeicosatrienoic acids by cytosolic epoxide hydrolase: substrate structural
determinants of asymmetric catalysis.

Arch. Biochem. Biophys.

316 (1995) 443–451. [PMID:

7840649

]

9. Haeggström, J., Meijer, J. and Rådmark, O. Leukotriene A

. Enzymatic conversion into 5,6-

dihydroxy-7,9,11,14-eicosatetraenoic acid by mouse liver cytosolic epoxide hydrolase.

J. Biol.

Chem.

261 (1986) 6332–6337. [PMID:

3009453

]

10. Newman, J.W., Morisseau, C. and Hammock, B.D. Epoxide hydrolases: their roles and

interactions with lipid metabolism.

Prog. Lipid Res.

44 (2005) 1–51. [PMID:

15748653

]

[EC 3.3.2.10 created 2006 (EC 3.3.2.3 part-incorporated 2006)]

EC 3.3.2.11

Common name: cholesterol-5,6-oxide hydrolase

Reaction: (1) 5,6α-epoxy-5α-cholestan-3β-ol + H

O = cholestane-3β-5α,6β-triol

(2) 5,6β-epoxy-5β-cholestan-3β-ol + H

O = cholestane-3β-5α,6β-triol

For diagram of reactions,

click here

Glossary: cholesterol = cholest-5-en-3β-ol

Other name(s): cholesterol-epoxide hydrolase; ChEH

Systematic name: 5,6α-epoxy-5α-cholestan-3β-ol hydrolase

Comments: The enzyme appears to work equally well with either epoxide as substrate [3]. The product is a

competitive inhibitor of the reaction. In vertebrates, five epoxide-hydrolase enzymes have been
identified to date:

EC 3.3.2.6

(leukotriene-A

hydrolase),

EC 3.3.2.7

(hepoxilin-epoxide hydrolase),

EC 3.3.2.9

(microsomal epoxide hydrolase),

EC 3.3.2.10

(soluble epoxide hydrolase) and EC

3.3.2.11 (cholesterol 5,6-oxide hydrolase) [3].

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References: 1. Levin, W., Michaud, D.P., Thomas, P.E. and Jerina, D.M. Distinct rat hepatic microsomal epoxide

hydrolases catalyze the hydration of cholesterol 5,6 α-oxide and certain xenobiotic alkene and
arene oxides.

Arch. Biochem. Biophys.

220 (1983) 485–494. [PMID:

6401984

]

2. Oesch, F., Timms, C.W., Walker, C.H., Guenthner, T.M., Sparrow, A., Watabe, T. and Wolf, C.R.

Existence of multiple forms of microsomal epoxide hydrolases with radically different substrate
specificities.

Carcinogenesis

5 (1984) 7–9. [PMID:

6690087

]

3. Sevanian, A. and McLeod, L.L. Catalytic properties and inhibition of hepatic cholesterol-epoxide

hydrolase.

J. Biol. Chem.

261 (1986) 54–59. [PMID:

3941086

]

4. Fretland, A.J. and Omiecinski, C.J. Epoxide hydrolases: biochemistry and molecular biology.

Chem. Biol. Interact.

129 (2000) 41–59. [PMID:

11154734

]

5. Newman, J.W., Morisseau, C. and Hammock, B.D. Epoxide hydrolases: their roles and

interactions with lipid metabolism.

Prog. Lipid Res.

44 (2005) 1–51. [PMID:

15748653

]

[EC 3.3.2.11 created 2006]

EC 3.4.21.87

Transferred entry: now

EC 3.4.23.49

, omptin. The enzyme is not a serine protease, as thought previously, but an

aspartate protease.

[EC 3.4.21.87 created 1993, deleted 2006]

EC 3.4.23.49

Recommended name: omptin

Reaction: Has a virtual requirement for Arg in the P1 position and a slightly less stringent preference for this

residue in the P1′ position, which can also contain Lys, Gly or Val.

Other name(s): protease VII; protease A; gene ompT proteins; ompT protease; protein a; Pla; protease VII;

protease A; OmpT

Comments: A product of the

ompT

gene of

Escherichia coli

, and associated with the outer membrane. Omptin

shows a preference for cleavage between consecutive basic amino acids, but is capable of
cleavage when P1′ is a non-basic residue [5,7]. Belongs in

peptidase family A26

Links to other databases: CAS registry number: 150770-86-8

References: 1. Grodberg, J., Lundrigan, M.D., Toledo, D.L., Mangel, W.F. and Dunn, J.J. Complete nucleotide

sequence and deduced amino acid sequence of the

ompT

gene of

Escherichia coli

K-12.

Nucleic Acids Res.

16 (1988) 1209 only. [PMID:

3278297

]

2. Sugimura, K. and Nishihara, T. Purification, characterization, and primary structure of

Escherichia coli

protease VII with specificity for paired basic residues: identity of protease VII

and

ompT

J. Bacteriol.

170 (1988) 5625–5632. [PMID:

3056908

]

3. Hanke, C., Hess, J., Schumacher, G. and Goebel, W. Processing by OmpT of fusion proteins

carrying the HlyA transport signal during secretion by the

Escherichia coli

hemolysin transport

system.

Mol. Gen. Genet.

233 (1992) 42–48. [PMID:

1603076

]

4. Dekker, N. Omptin. In: Barrett, A.J., Rawlings, N.D. and Woessner, J.F. (Eds),

Handbook of

Proteolytic Enzymes

, 2nd edn, Elsevier, London, 2004, pp. 212–216.

5. Vandeputte-Rutten, L., Kramer, R.A., Kroon, J., Dekker, N., Egmond, M.R. and Gros, P. Crystal

structure of the outer membrane protease OmpT from

Escherichia coli

suggests a novel catalytic

site.

EMBO J.

20 (2001) 5033–5039. [PMID:

11566868

]

6. Kramer, R.A., Vandeputte-Rutten, L., de Roon, G.J., Gros, P., Dekker, N. and Egmond, M.R.

Identification of essential acidic residues of outer membrane protease OmpT supports a novel
active site.

FEBS Lett.

505 (2001) 426–430. [PMID:

11576541

]

7. McCarter, J.D., Stephens, D., Shoemaker, K., Rosenberg, S., Kirsch, J.F. and Georgiou, G.

Substrate specificity of the

Escherichia coli

outer membrane protease OmpT.

J. Bacteriol.

186

(2004) 5919–5925. [PMID:

15317797

]

[EC 3.4.23.49 created 1993 as EC 3.4.21.87, transferred 2006 to EC 3.4.23.49]

EC 3.5.1.94

Common name: γ-glutamyl-γ-aminobutyrate hydrolase

Reaction: 4-(γ-glutamylamino)butanoate + H

O = 4-aminobutanoate +

-glutamate

Other name(s): γ-glutamyl-GABA hydrolase; PuuD; YcjL

Systematic name: 4-(γ-glutamylamino)butanoate amidohydrolase

Comments: Forms part of a novel putrescine-utilizing pathway in

Escherichia coli

, in which it has been

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hypothesized that putrescine is first glutamylated to form γ-glutamylputrescine, which is oxidized to
4-(γ-glutamylamino)butanal and then to 4-(γ-glutamylamino)butanoate. The enzyme can also
catalyse the reactions of

EC 3.5.1.35

(

-glutaminase) and

EC 3.5.1.65

(theanine hydrolase).

References: 1. Kurihara, S., Oda, S., Kato, K., Kim, H.G., Koyanagi, T., Kumagai, H. and Suzuki, H. A novel

putrescine utilization pathway involves γ-glutamylated intermediates of

Escherichia coli

K-12.

Biol. Chem.

280 (2005) 4602–4608. [PMID:

15590624

]

[EC 3.5.1.94 created 2006]

EC 3.5.1.95

Common name:

-malonylurea hydrolase

Reaction: 3-oxo-3-ureidopropanoate + H

O = malonate + urea

For pyrimidine catabolism,

click here

Other name(s): ureidomalonase

Systematic name: 3-oxo-3-ureidopropanoate amidohydrolase (urea- and malonate-forming)

Comments: Forms part of the oxidative pyrimidine-degrading pathway in some microorganisms, along with

1.17.99.4

(uracil/thymine dehydrogenase) and

EC 3.5.2.1

(barbiturase).

References: 1. Soong, C.L., Ogawa, J. and Shimizu, S. Novel amidohydrolytic reactions in oxidative pyrimidine

metabolism: analysis of the barbiturase reaction and discovery of a novel enzyme,
ureidomalonase.

Biochem. Biophys. Res. Commun.

286 (2001) 222–226. [PMID:

11485332

]

2. Soong, C.L., Ogawa, J., Sakuradani, E. and Shimizu, S. Barbiturase, a novel zinc-containing

amidohydrolase involved in oxidative pyrimidine metabolism.

J. Biol. Chem.

277 (2002) 7051–

7058. [PMID:

11748240

]

[EC 3.5.1.95 created 2006]

EC 3.5.1.96

Common name: succinylglutamate desuccinylase

Reaction:

-succinyl-

-glutamate + H

O = succinate +

-glutamate

For diagram of arginine catabolism,

click here

Other name(s):

-succinylglutamate desuccinylase; SGDS; AstE

Systematic name:

-succinyl-

-glutamate amidohydrolase

Comments: Requires Co

for maximal activity [1]. 2-

-Acetylglutamate is not a substrate. This is the final

enzyme in the arginine succinyltransferase (AST) pathway for the catabolism of arginine [1]. This
pathway converts the carbon skeleton of arginine into glutamate, with the concomitant production of
ammonia and conversion of succinyl-CoA into succinate and CoA. The five enzymes involved in
this pathway are

EC 2.3.1.109

(arginine

-succinyltransferase),

EC 3.5.3.23

(

-succinylarginine

dihydrolase),

EC 2.6.1.11

(acetylornithine transaminase),

EC 1.2.1.71

(succinylglutamate-

semialdehyde dehydrogenase) and EC 3.5.1.96 (succinylglutamate desuccinylase).

References: 1. Vander Wauven, C. and Stalon, V. Occurrence of succinyl derivatives in the catabolism of

arginine in

Pseudomonas cepacia

J. Bacteriol.

164 (1985) 882–886. [PMID:

2865249

]

2. Cunin, R., Glansdorff, N., Pierard, A. and Stalon, V. Biosynthesis and metabolism of arginine in

bacteria.

Microbiol. Rev.

50 (1986) 314–352. [PMID:

3534538

]

3. Cunin, R., Glansdorff, N., Pierard, A. and Stalon, V. Erratum report: Biosynthesis and

metabolism of arginine in bacteria.

Microbiol. Rev.

51 (1987) 178 only.

4. Itoh, Y. Cloning and characterization of the

aru

genes encoding enzymes of the catabolic

arginine succinyltransferase pathway in

Pseudomonas aeruginosa

J. Bacteriol.

179 (1997)

7280–7290. [PMID:

9393691

]

5. Schneider, B.L., Kiupakis, A.K. and Reitzer, L.J. Arginine catabolism and the arginine

succinyltransferase pathway in

Escherichia coli

J. Bacteriol.

180 (1998) 4278–4286. [PMID:

9696779

]

[EC 3.5.1.96 created 2006]

*EC 3.5.2.1

Common name: barbiturase

Reaction: barbiturate + H

O = 3-oxo-3-ureidopropanoate

For diagram of pyrimidine catabolism,

click here

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Glossary: barbiturate = 6-hydroxyuracil

Systematic name: barbiturate amidohydrolase (3-oxo-3-ureidopropanoate-forming)

Comments: Contains zinc and is specific for barbiturate as substrate [3]. Forms part of the oxidative pyrimidine-

degrading pathway in some microorganisms, along with

EC 1.17.99.4

(uracil/thymine

dehydrogenase) and

EC 3.5.1.95

(

-malonylurea hydrolase). It was previously thought that the

end-products of the reaction were malonate and urea but this has since been disproved [2]. May be
involved in the regulation of pyrimidine metabolism, along with

EC 2.4.2.9

, uracil

phosphoribosyltransferase.

Links to other databases:

BRENDA

ERGO

EXPASY

IUBMB

KEGG

, CAS registry number: 9025-16-5

References: 1. Hayaishi, O. and Kornberg, A. Metabolism of cytosine, thymine, uracil, and barbituric acid by

bacterial enzymes.

J. Biol. Chem.

197 (1952) 717–723. [PMID:

12981104

]

2. Soong, C.L., Ogawa, J. and Shimizu, S. Novel amidohydrolytic reactions in oxidative pyrimidine

metabolism: analysis of the barbiturase reaction and discovery of a novel enzyme,
ureidomalonase.

Biochem. Biophys. Res. Commun.

286 (2001) 222–226. [PMID:

11485332

]

3. Soong, C.L., Ogawa, J., Sakuradani, E. and Shimizu, S. Barbiturase, a novel zinc-containing

amidohydrolase involved in oxidative pyrimidine metabolism.

J. Biol. Chem.

277 (2002) 7051–

7058. [PMID:

11748240

]

[EC 3.5.2.1 created 1961, modified 2006]

EC 3.5.3.23

Common name:

-succinylarginine dihydrolase

Reaction: 2-

-succinyl-

-arginine + 2 H

O = 2-

-succinyl-

-ornithine + 2 NH

+ CO

For diagram of arginine catabolism,

click here

Other name(s):

-succinylarginine dihydrolase; arginine succinylhydrolase; SADH; AruB; AstB;

-succinyl-

arginine iminohydrolase (decarboxylating)

Systematic name: 2-

-succinyl-

-arginine iminohydrolase (decarboxylating)

Comments: Arginine, 2-

-acetylarginine and 2-

-glutamylarginine do not act as substrates [3]. This is the

second enzyme in the arginine succinyltransferase (AST) pathway for the catabolism of arginine [1].
This pathway converts the carbon skeleton of arginine into glutamate, with the concomitant
production of ammonia and conversion of succinyl-CoA into succinate and CoA. The five enzymes
involved in this pathway are

EC 2.3.1.109

(arginine

-succinyltransferase), EC 3.5.3.23 (

succinylarginine dihydrolase),

EC 2.6.1.81

(succinylornithine transaminase),

EC 1.2.1.71

(succinylglutamate semialdehyde dehydrogenase) and

EC 3.5.1.96

(succinylglutamate

desuccinylase).

References: 1. Schneider, B.L., Kiupakis, A.K. and Reitzer, L.J. Arginine catabolism and the arginine

succinyltransferase pathway in

Escherichia coli

J. Bacteriol.

180 (1998) 4278–4286. [PMID:

9696779

]

2. Tocilj, A., Schrag, J.D., Li, Y., Schneider, B.L., Reitzer, L., Matte, A. and Cygler, M. Crystal

structure of

-succinylarginine dihydrolase AstB, bound to substrate and product, an enzyme

from the arginine catabolic pathway of

Escherichia coli

J. Biol. Chem.

280 (2005) 15800–15808.

[PMID:

15703173

]

3. Vander Wauven, C. and Stalon, V. Occurrence of succinyl derivatives in the catabolism of

arginine in

Pseudomonas cepacia

J. Bacteriol.

164 (1985) 882–886. [PMID:

2865249

]

4. Cunin, R., Glansdorff, N., Pierard, A. and Stalon, V. Biosynthesis and metabolism of arginine in

bacteria.

Microbiol. Rev.

50 (1986) 314–352. [PMID:

3534538

]

5. Itoh, Y. Cloning and characterization of the

aru

genes encoding enzymes of the catabolic

arginine succinyltransferase pathway in

Pseudomonas aeruginosa

J. Bacteriol.

179 (1997)

7280–7290. [PMID:

9393691

]

[EC 3.5.3.23 created 2006]

*EC 3.6.3.5

Common name: Zn

-exporting ATPase

Reaction: ATP + H

O + Zn

= ADP + phosphate + Zn

out

Other name(s): Zn(II)-translocating P-type ATPase; P1B-type ATPase; AtHMA4

Systematic name: ATP phosphohydrolase (Zn

-exporting)

Comments: A P-type ATPase that undergoes covalent phosphorylation during the transport cycle. This enzyme

also exports Cd

and Pb

Links to other databases:

BRENDA

ERGO

EXPASY

IUBMB

KEGG

PDB

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References: 1. Beard, S.J., Hashim, R., Membrillo-Hernández, J., Hughes, M.N. and Poole, R.K. Zinc(II)

tolerance in

Escherichia coli

K-12: evidence that the

zntA

gene (

o732

) encodes a cation

transport ATPase.

Mol. Microbiol.

25 (1997) 883–891. [PMID:

9364914

]

2. Rensing, C., Mitra, B. and Rosen, B.P. The

zntA

gene of

Escherichia coli

encodes a Zn(II)-

translocating P-type ATPase.

Proc. Natl. Acad. Sci. USA

94 (1997) 14326–14331. [PMID:

9405611

]

3. Rensing, C., Sun, Y., Mitra, B. and Rosen, B.P. Pb(II)-translocating P-type ATPases.

J. Biol.

Chem.

273 (1998) 32614–32617. [PMID:

9830000

]

4. Mills, R.F., Francini, A., Ferreira da Rocha, P.S., Baccarini, P.J., Aylett, M., Krijger, G.C. and

Williams, L.E. The plant P1B-type ATPase AtHMA4 transports Zn and Cd and plays a role in
detoxification of transition metals supplied at elevated levels.

FEBS Lett.

579 (2005) 783–791.

[PMID:

15670847

]

5. Eren, E. and Argüello, J.M. Arabidopsis HMA2, a divalent heavy metal-transporting P(IB)-type

ATPase, is involved in cytoplasmic Zn

homeostasis.

Plant Physiol.

136 (2004) 3712–3723.

[PMID:

15475410

]

[EC 3.6.3.5 created 2000, modified 2001, modified 2006]

*EC 3.6.3.44

Common name: xenobiotic-transporting ATPase

Reaction: ATP + H

O + xenobiotic

= ADP + phosphate + xenobiotic

out

Other name(s): multidrug-resistance protein; MDR protein; P-glycoprotein; pleiotropic-drug-resistance protein; PDR

protein; steroid-transporting ATPase; ATP phosphohydrolase (steroid-exporting)

Systematic name: ATP phosphohydrolase (xenobiotic-exporting)

Comments: ABC-type (ATP-binding cassette-type) ATPase, characterized by the presence of two similar ATP-

binding domains. Does not undergo phosphorylation during the transport process. The enzyme from
Gram-positive bacteria and eukaryotic cells export a number of drugs, with unusual specificity,
covering various groups of unrelated substances, while ignoring some that are closely related
structurally. Several distinct enzymes may be present in a single eukaryotic cell. Many of them
transport glutathione—drug conjugates. Some also show some 'flippase' (phospholipid-
translocating ATPase;

EC 3.6.3.1

) activity.

Links to other databases:

BRENDA

ERGO

EXPASY

IUBMB

KEGG

References: 1. Bellamy, W.T. P-glycoproteins and multidrug resistance.

Annu. Rev. Pharmac. Toxicol.

(1996) 161–183. [PMID:

8725386

]

2. Frijters, C.M., Ottenhoff, R., Van Wijland, M.J., Van Nieuwkerk, C., Groen, A.K. and Oude-

Elferink, R.P. Influence of bile salts on hepatic mdr2 P-glycoprotein expression.

Adv. Enzyme

Regul.

36 (1996) 351–363. [PMID:

8869755

]

3. Keppler, D., König, J. and Buchler, M. The canalicular multidrug resistance protein,

cMRP/MRP2, a novel conjugate export pump expressed in the apical membrane of hepatocytes.

Adv. Enzyme Regul.

37 (1997) 321–333. [PMID:

9381978

]

4. Loe, D.W., Deeley, R.G. and Cole, S.P. Characterization of vincristine transport by the M

190,000 multidrug resistance protein (MRP): evidence for cotransport with reduced glutathione.

Cancer Res.

58 (1998) 5130–5136. [PMID:

9823323

]

5. van Veen, H.W. and Konings, W.N. The ABC family of multidrug transporters in microorganisms.

Biochim. Biophys. Acta

1365 (1998) 31–36. [PMID:

9693718

]

6. Griffiths, J.K. and Sansom, C.E.

The Transporter Factsbook

, Academic Press, San Diego, 1998.

7. Prasad, R., De Wergifosse, P., Goffeau, A. and Balzi, E. Molecular cloning and characterization

of a novel gene of

Candida albicans

, CDR1, conferring multiple resistance to drugs and

antifungals.

Curr. Genet.

27 (1995) 320–329. [PMID:

7614555

]

8. Nagao, K., Taguchi, Y., Arioka, M., Kadokura, H., Takatsuki, A., Yoda, K. and Yamasaki, M.

bfr1

, a novel gene of

Schizosaccharomyces pombe

which confers brefeldin A resistance, is

structurally related to the ATP-binding cassette superfamily.

J. Bacteriol.

177 (1995) 1536–1543.

[PMID:

7883711

]

9. Mahé, Y., Lemoine, Y. and Kuchler, K. The ATP-binding cassette transporters Pdr5 and Snq2 of

Saccharomyces cerevisiae

can mediate transport of steroids in vivo.

J. Biol. Chem.

271 (1996)

25167–25172. [PMID:

8810273

]

[EC 3.6.3.44 created 2000 (EC 3.6.3.45 incorporated 2006), modified 2006]

EC 3.6.3.45

Deleted entry: steroid-transporting ATPase. Now included with

EC 3.6.3.44

, xenobiotic-transporting ATPase

[EC 3.6.3.45 created 2000, deleted 2006]

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*EC 4.1.1.21

Common name: phosphoribosylaminoimidazole carboxylase

Reaction: 5-amino-1-(5-phospho-

-ribosyl)imidazole-4-carboxylate = 5-amino-1-(5-phospho-

ribosyl)imidazole + CO

For diagram of the late stages of purine biosynthesis,

click here

Other name(s): 5-phosphoribosyl-5-aminoimidazole carboxylase; 5-amino-1-ribosylimidazole 5-phosphate

carboxylase; AIR carboxylase; 1-(5-phosphoribosyl)-5-amino-4-imidazolecarboxylate carboxy-
lyase; ADE2; class II PurE

Systematic name: 5-amino-1-(5-phospho-

-ribosyl)imidazole-4-carboxylate carboxy-lyase

Comments: While this is the reaction that occurs in vertebrates during purine biosynthesis, two enzymes are

required to carry out the same reaction in

Escherichia coli

, namely

EC 6.3.4.18

, 5-

(carboxyamino)imidazole ribonucleotide synthase and

EC 5.4.99.18

, 5-(carboxyamino)imidazole

ribonucleotide mutase [3]. 5-Carboxyamino-1-(5-phospho-

-ribosyl)imidazole is not a substrate.

Links to other databases:

BRENDA

ERGO

EXPASY

IUBMB

KEGG

PDB

, CAS registry number: 9032-04-6

References: 1. Lukens, L.N. and Buchanan, J.M. Biosynthesis of purines. XXIV. The enzymatic synthesis of 5-

amino-1-ribosyl-4-imidazolecarboxylic acid 5′-phosphate from 5-amino-1-ribosylimidazole 5′-
phosphate and carbon dioxide.

J. Biol. Chem.

234 (1959) 1799–1805. [PMID:

13672967

]

2. Firestine, S.M., Poon, S.W., Mueller, E.J., Stubbe, J. and Davisson, V.J. Reactions catalyzed by

5-aminoimidazole ribonucleotide carboxylases from

Escherichia coli

and

Gallus gallus

: a case

for divergent catalytic mechanisms.

Biochemistry

33 (1994) 11927–11934. [PMID:

7918411

]

3. Firestine, S.M., Misialek, S., Toffaletti, D.L., Klem, T.J., Perfect, J.R. and Davisson, V.J.

Biochemical role of the

Cryptococcus neoformans

ADE2 protein in fungal de novo purine

biosynthesis.

Arch. Biochem. Biophys.

351 (1998) 123–134. [PMID:

9500840

]

[EC 4.1.1.21 created 1961, modified 2000, modified 2006]

EC 4.1.1.86

Common name: diaminobutyrate decarboxylase

Reaction:

-2,4-diaminobutanoate = propane-1,3-diamine + CO

For diagram of ectoine biosynthesis,

click here

Other name(s): DABA DC;

-2,4-diaminobutyrate decarboxylase

Systematic name:

-2,4-diaminobutanoate carboxy-lyase

Comments: A pyridoxal-phosphate protein that requires a divalent cation for activity [1]. 4-

-Acetyl-

-2,4-

diaminobutanoate, 2,3-diaminopropanoate, ornithine and lysine are not substrates. Found in the
proteobacteria

Haemophilus influenzae

and

Acinetobacter baumannii

. In the latter, it is a product of

the

ddc

gene that also encodes

EC 2.6.1.76

, diaminobutyrate—2-oxoglutarate transaminase, which

can supply the substrate for the decarboxylase.

References: 1. Yamamoto, S., Tsuzaki, Y., Tougou, K. and Shinoda, S. Purification and characterization of

2,4-diaminobutyrate decarboxylase from

Acinetobacter calcoaceticus

J. Gen. Microbiol.

138

(1992) 1461–1465. [PMID:

1512577

]

2. Ikai, H. and Yamamoto, S. Cloning and expression in

Escherichia coli

of the gene encoding a

novel

-2,4-diaminobutyrate decarboxylase of

Acinetobacter baumannii

FEMS Microbiol. Lett.

124 (1994) 225–228. [PMID:

7813892

]

3. Ikai, H. and Yamamoto, S. Identification and analysis of a gene encoding

-2,4-

diaminobutyrate:2-ketoglutarate 4-aminotransferase involved in the 1,3-diaminopropane
production pathway in

Acinetobacter baumannii

J. Bacteriol.

179 (1997) 5118–5125. [PMID:

9260954

]

[EC 4.1.1.86 created 2006]

*EC 4.1.2.8

Common name: indole-3-glycerol-phosphate lyase

Reaction: (1

)-1-

-(indol-3-yl)glycerol 3-phosphate = indole +

-glyceraldehyde 3-phosphate

For diagram of reaction,

click here

Other name(s): tryptophan synthase α; TSA; indoleglycerolphosphate aldolase; indole glycerol phosphate

hydrolase; indole synthase; indole-3-glycerolphosphate

-glyceraldehyde-3-phosphate-lyase;

indole-3-glycerol phosphate lyase; IGL; BX1

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Systematic name: (1

)-1-

-(indol-3-yl)glycerol 3-phosphate

-glyceraldehyde-3-phosphate-lyase

Comments: Forms part of the defence mechanism against insects and microbial pathogens in the grass family,

Gramineae, where it catalyses the first committed step in the formation of the cyclic hydroxamic
acids 2,4-dihydroxy-2

-1,4-benzoxazin-3(4

)-one (DIBOA) and 2,4-dihydroxy-7-methoxy-2

-1,4-

benzoxazin-3(4

)-one (DIMBOA) [1]. This enzyme resembles the α-subunit of

EC 4.2.1.20

tryptophan synthase [3], for which, (1

)-1-

-(indol-3-yl)glycerol 3-phosphate is also a

substrate, but, unlike tryptophan synthase, its activity is independent of the β-subunit and free
indole is released [2].

References: 1. Yanofsky, C. The enzymatic conversion of anthranilic acid to indole.

J. Biol. Chem.

223 (1956)

171–184. [PMID:

13376586

]

2. Frey, M., Chomet, P., Glawischnig, E., Stettner, C., Grün, S., Winklmair, A., Eisenreich, W.,

Bacher, A., Meeley, R.B., Briggs, S.P., Simcox, K. and Gierl, A. Analysis of a chemical plant
defense mechanism in grasses.

Science

277 (1997) 696–699.

3. Frey, M., Stettner, C., Paré, P.W., Schmelz, E.A., Tumlinson, J.H. and Gierl, A. An herbivore

elicitor activates the gene for indole emission in maize.

Proc. Natl. Acad. Sci. USA

97 (2000)

14801–14806. [PMID:

11106389

]

4. Melanson, D., Chilton, M.D., Masters-Moore, D. and Chilton, W.S. A deletion in an indole

synthase gene is responsible for the DIMBOA-deficient phenotype of

bxbx

maize.

Proc. Natl.

Acad. Sci. USA

94 (1997) 13345–13350. [PMID:

9371848

]

[EC 4.1.2.8 created 1961, deleted 1972, reinstated 2006]

EC 4.1.3.39

Common name: 4-hydroxy-2-oxovalerate aldolase

Reaction: 4-hydroxy-2-oxopentanoate = pyruvate + acetaldehyde

Glossary: valerate = pentanoate

Other name(s): 4-hydroxy-2-ketovalerate aldolase; HOA; DmpG; 4-hydroxy-2-oxovalerate pyruvate-lyase

Systematic name: 4-hydroxy-2-oxopentanoate pyruvate-lyase

Comments: Requires Mn

for maximal activity [1]. The enzyme from

Pseudomonas putida

is also stimulated by

the presence of NADH [1]. In

Pseudomonas

species, this enzyme forms part of a bifunctional

enzyme with

EC 1.2.1.10

, acetaldehyde dehydrogenase (acetylating). It catalyses the penultimate

step in the meta-cleavage pathway for the degradation of phenols, cresols and catechol [1].

References: 1. Manjasetty, B.A., Powlowski, J. and Vrielink, A. Crystal structure of a bifunctional aldolase-

dehydrogenase: sequestering a reactive and volatile intermediate.

Proc. Natl. Acad. Sci. USA

100 (2003) 6992–6997. [PMID:

12764229

]

2. Powlowski, J., Sahlman, L. and Shingler, V. Purification and properties of the physically

associated meta-cleavage pathway enzymes 4-hydroxy-2-ketovalerate aldolase and aldehyde
dehydrogenase (acylating) from

Pseudomonas

sp. strain CF600.

J. Bacteriol.

175 (1993) 377–

385. [PMID:

8419288

]

3. Manjasetty, B.A., Croteau, N., Powlowski, J. and Vrielink, A. Crystallization and preliminary X-ray

analysis of

dmpFG

-encoded 4-hydroxy-2-ketovalerate aldolase—aldehyde dehydrogenase

(acylating) from

Pseudomonas

sp. strain CF600.

Acta Crystallogr. D Biol. Crystallogr.

57 (2001)

582–585. [PMID:

11264589

]

[EC 4.1.3.39 created 2006]

*EC 4.2.1.60

Common name: 3-hydroxydecanoyl-[acyl-carrier-protein] dehydratase

Reaction: (1) (3

)-3-hydroxydecanoyl-[acyl-carrier-protein] =

trans

-dec-2-enoyl-[acyl-carrier-protein] + H

(2) (3

)-3-hydroxydecanoyl-[acyl-carrier-protein] =

cis

-dec-3-enoyl-[acyl-carrier-protein] + H

Other name(s):

-3-hydroxydecanoyl-[acyl-carrier protein] dehydratase; 3-hydroxydecanoyl-acyl carrier protein

dehydrase; 3-hydroxydecanoyl-acyl carrier protein dehydratase; β-hydroxydecanoyl thioester
dehydrase; β-hydroxydecanoate dehydrase; β-hydroxydecanoyl thiol ester dehydrase; FabA; β-
hydroxyacyl-acyl carrier protein dehydratase; HDDase; β-hydroxyacyl-ACP dehydrase

Systematic name: (3

)-3-hydroxydecanoyl-[acyl-carrier-protein] hydro-lyase

Comments: Specific for C

chain length.

Links to other databases:

BRENDA

ERGO

EXPASY

IUBMB

KEGG

PDB

, CAS registry number: 9030-79-9

References: 1. Kass, L.R., Brock, D.J.H. and Bloch, K. β-Hydroxydecanoyl thioester dehydrase. I. Purification

and properties.

J. Biol. Chem.

242 (1967) 4418–4431. [PMID:

4863739

]

2. Brock, D.J.H., Kass, L.R. and Bloch, K. β-Hydroxydecanoyl thioester dehydrase. II. Mode of

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action.

J. Biol. Chem.

242 (1967) 4432–4440. [PMID:

4863740

]

3. Sharma, A., Henderson, B.S., Schwab, J.M. and Smith, J.L. Crystallization and preliminary X-ray

analysis of β-hydroxydecanoyl thiol ester dehydrase from

Escherichia coli

J. Biol. Chem.

265

(1990) 5110–5112. [PMID:

2180957

]

4. Magnuson, K., Jackowski, S., Rock, C.O. and Cronan, J.E., Jr. Regulation of fatty acid

biosynthesis in

Escherichia coli

Microbiol. Rev.

57 (1993) 522–542. [PMID:

8246839

]

5. Bloch, K. Enzymatic synthesis of monounsaturated fatty acids.

Acc. Chem. Res.

2 (1969) 193–

202.

6. Wang, H. and Cronan, J.E. Functional replacement of the FabA and FabB proteins of

Escherichia coli

fatty acid synthesis by

Enterococcus faecalis

FabZ and FabF homologues.

Biol. Chem.

279 (2004) 34489–34495. [PMID:

15194690

]

7. Cronan, J.E., Jr. and Rock, C.O. Biosynthesis of membrane lipids. In: Neidhardt, F.C. (Ed.),

Escherichia coli and Salmonella: Cellular and Molecular Biology

, 2nd edn, vol. 1, ASM Press,

Washington, DC, 1996, pp. 612–636.

[EC 4.2.1.60 created 1972, modified 2006]

EC 4.2.1.108

Common name: ectoine synthase

Reaction: 4-

-acetyl-

-2,4-diaminobutanoate =

-ectoine + H

For diagram of ectoine biosynthesis,

click here

Glossary: ectoine = (4

)-2-methyl-1,4,5,6-tetrahydropyrimidine-4-carboxylate

Other name(s):

-acetyldiaminobutyrate dehydratase;

-acetyldiaminobutanoate dehydratase;

-ectoine synthase;

EctC;

-acetyl-

-2,4-diaminobutanoate hydro-lyase

Systematic name: 4-

-acetyl-

-2,4-diaminobutanoate hydro-lyase

Comments: Ectoine is an osmoprotectant that is found in halophilic eubacteria. This is the third enzyme in the

ectoine-biosynthesis pathway, the other enzymes involved being

EC 2.6.1.76

, diaminobutyrate—2-

oxoglutarate transaminase and

EC 2.3.1.178

, diaminobutyrate acetyltransferase [1,2].

References: 1. Peters, P., Galinski, E.A. and Truper, H.G. The biosynthesis of ectoine.

FEMS Microbiol. Lett.

(1990) 157–162.

2. Ono, H., Sawada, K., Khunajakr, N., Tao, T., Yamamoto, M., Hiramoto, M., Shinmyo, A., Takano,

M. and Murooka, Y. Characterization of biosynthetic enzymes for ectoine as a compatible solute
in a moderately halophilic eubacterium,

Halomonas elongata

J. Bacteriol.

181 (1999) 91–99.

[PMID:

9864317

]

3. Kuhlmann, A.U. and Bremer, E. Osmotically regulated synthesis of the compatible solute ectoine

Bacillus pasteurii

and related

Bacillus

spp.

Appl. Environ. Microbiol.

68 (2002) 772–783.

[PMID:

11823218

]

4. Louis, P. and Galinski, E.A. Characterization of genes for the biosynthesis of the compatible

solute ectoine from

Marinococcus halophilus

and osmoregulated expression in

Escherichia coli

Microbiology

143 (1997) 1141–1149. [PMID:

9141677

]

[EC 4.2.1.108 created 2006]

*EC 4.2.3.9

Common name: aristolochene synthase

Reaction: (1) 2-

trans

,6-

trans

-farnesyl diphosphate = aristolochene + diphosphate

(2) 2-

trans

,6-

trans

-farnesyl diphosphate = (+)-(10

)-germacrene A + diphosphate

For diagram of germacrene-derived sesquiterpenoid biosynthesis,

click here

Other name(s): sesquiterpene cyclase;

trans

-farnesyl diphosphate aristolochene-lyase;

trans

-farnesyl-

diphosphate diphosphate-lyase (cyclizing, aristolochene-forming)

Systematic name: 2-

trans

,6-

trans

-farnesyl-diphosphate diphosphate-lyase (cyclizing, aristolochene-forming)

Comments: The initial internal cyclization produces the monocyclic intermediate germacrene A; further

cyclization and methyl transfer converts the intermediate into aristolochene. While in some species
germacrene A remains as an enzyme-bound intermediate, it has been shown to be a minor product
of the reaction in

Penicillium roqueforti

[5] (see also

EC 4.2.3.23

, germacrene-A synthase). The

enzyme from

Penicillium roqueforti

requires Mg

and Mn

for activity. Aristolochene is the likely

parent compound for a number of sesquiterpenes produced by filamentous fungi.

Links to other databases:

BRENDA

ERGO

EXPASY

IUBMB

KEGG

PDB

References: 1. Cane, D.E., Prabhakaran, P.C., Oliver, J.S. and McIlwaine, D.B. Aristolochene biosynthesis.

Stereochemistry of the deprotonation steps in the enzymatic cyclization of farnesyl

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pyrophosphate.

J. Am. Chem. Soc.

112 (1990) 3209–3210.

2. Cane, D.E., Prabhakaran, P.C., Salaski, E.J., Harrison, P.M.H., Noguchi, H. and Rawlings, B.J.

Aristolochene biosynthesis and enzymatic cyclization of farnesyl pyrophosphate.

J. Am. Chem.

Soc.

111 (1989) 8914–8916.

3. Hohn, T.M. and Plattner, R.D. Purification and characterization of the sesquiterpene cyclase

aristolochene synthase from

Penicillium roqueforti

Arch. Biochem. Biophys.

272 (1989) 137–

143. [PMID:

2544140

]

4. Proctor, R.H. and Hohn, T.M. Aristolochene synthase. Isolation, characterization, and bacterial

expression of a sesquiterpenoid biosynthetic gene (

Ari1

) from

Penicillium roqueforti

J. Biol.

Chem.

268 (1993) 4543–4548. [PMID:

8440737

]

5. Calvert, M.J., Ashton, P.R. and Allemann, R.K. Germacrene A is a product of the aristolochene

synthase-mediated conversion of farnesylpyrophosphate to aristolochene.

J. Am. Chem. Soc.

124 (2002) 11636–11641. [PMID:

12296728

]

[EC 4.2.3.9 created 1992 as EC 2.5.1.40, transferred 1999 to EC 4.1.99.7, transferred 2000 to EC 4.2.3.9, modified 2006]

EC 4.2.3.22

Common name: germacradienol synthase

Reaction: (1) 2-

trans

,6-

trans

-farnesyl diphosphate + H

O = (1

)-germacra-1(10),5-dien-11-ol +

diphosphate
(2) 2-

trans

,6-

trans

-farnesyl diphosphate = (-)-(7

)-germacrene D

Other name(s): germacradienol/germacrene-D synthase

Systematic name: 2-

trans

,6-

trans

-farnesyl-diphosphate diphosphate-lyase [(1

)-germacra-1(10),5-dien-

11-ol-forming]

Comments: Requires Mg

for activity. H-1

of farnesyl diphosphate is lost in the formation of (1

germacra-1(10),5-dien-11-ol. Formation of (-)-germacrene D involves a stereospecific 1,3-hydride
shift of H-1

of farnesyl diphosphate. Both products are formed from a common intermediate [2].

Other enzymes produce germacrene D as the sole product using a different mechanism. The
enzyme mediates a key step in the biosynthesis of geosmin, a widely occurring metabolite of many
streptomycetes, bacteria and fungi [2].

References: 1. Cane, D.E. and Watt, R.M. Expression and mechanistic analysis of a germacradienol synthase

from

Streptomyces coelicolor

implicated in geosmin biosynthesis.

Proc. Natl. Acad. Sci. USA

100

(2003) 1547–1551. [PMID:

12556563

]

2. He, X. and Cane, D.E. Mechanism and stereochemistry of the germacradienol/germacrene D

synthase of

Streptomyces coelicolor

A3(2).

J. Am. Chem. Soc.

126 (2004) 2678–2679. [PMID:

14995166

]

3. Gust, B., Challis, G.L., Fowler, K., Kieser, T. and Chater, K.F. PCR-targeted

Streptomyces

gene

replacement identifies a protein domain needed for biosynthesis of the sesquiterpene soil odor
geosmin.

Proc. Natl. Acad. Sci. USA

100 (2003) 1541–1546. [PMID:

12563033

]

[EC 4.2.3.22 created 2006]

EC 4.2.3.23

Common name: germacrene-A synthase

Reaction: 2-

trans

,6-

trans

-farnesyl diphosphate = (+)-(10

)-germacrene A + diphosphate

For diagram of germacrene-derived sesquiterpenoid biosynthesis,

click here

Other name(s): germacrene A synthase; (+)-germacrene A synthase; (+)-(10

)-germacrene A synthase; GAS

Systematic name: 2-

trans

,6-

trans

-farnesyl-diphosphate diphosphate-lyase (germacrene-A-forming)

Comments: Requires Mg

for activity. While germacrene A is an enzyme-bound intermediate in the

biosynthesis of a number of phytoalexins, e.g.

EC 4.2.3.9

(aristolochene synthase) from some

species and

EC 4.2.3.21

(vetispiradiene synthase), it is the sole sesquiterpenoid product formed in

chicory [1].

References: 1. Bouwmeester, H.J., Kodde, J., Verstappen, F.W., Altug, I.G., de Kraker, J.W. and Wallaart, T.E.

Isolation and characterization of two germacrene A synthase cDNA clones from chicory.

Plant

Physiol.

129 (2002) 134–144. [PMID:

12011345

]

2. Prosser, I., Phillips, A.L., Gittings, S., Lewis, M.J., Hooper, A.M., Pickett, J.A. and Beale, M.H.

(+)-(10

)-Germacrene A synthase from goldenrod,

Solidago canadensis

; cDNA isolation,

bacterial expression and functional analysis.

Phytochemistry

60 (2002) 691–702. [PMID:

12127586

]

3. de Kraker, J.W., Franssen, M.C., de Groot, A., König, W.A. and Bouwmeester, H.J. (+)-

Germacrene A biosynthesis . The committed step in the biosynthesis of bitter sesquiterpene

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lactones in chicory.

Plant Physiol.

117 (1998) 1381–1392. [PMID:

9701594

]

4. Calvert, M.J., Ashton, P.R. and Allemann, R.K. Germacrene A is a product of the aristolochene

synthase-mediated conversion of farnesylpyrophosphate to aristolochene.

J. Am. Chem. Soc.

124 (2002) 11636–11641. [PMID:

12296728

]

5. Chang, Y.J., Jin, J., Nam, H.Y. and Kim, S.U. Point mutation of (+)-germacrene A synthase from

Ixeris dentata

Biotechnol. Lett.

27 (2005) 285–288. [PMID:

15834787

]

[EC 4.2.3.23 created 2006]

EC 4.2.3.24

Common name: amorpha-4,11-diene synthase

Reaction: 2-

trans

,6-

trans

-farnesyl diphosphate = amorpha-4,11-diene + diphosphate

Other name(s): amorphadiene synthase

Systematic name: 2-

trans

,6-

trans

-farnesyl-diphosphate diphosphate-lyase (amorpha-4,11-diene-forming)

Comments: Requires Mg

and Mn

for activity. This is a key enzyme in the biosynthesis of the antimalarial

endoperoxide artemisinin [3]. Catalyses the formation of both olefinic [e.g. amorpha-4,11-diene,
amorpha-4,7(11)-diene, γ-humulene and β-sesquiphellandrene] and oxygenated (e.g. amorpha-4-
en-7-ol) sesquiterpenes, with amorpha-4,11-diene being the major product. When geranyl
diphosphate is used as a substrate, no monoterpenes are produced [2].

References: 1. Wallaart, T.E., Bouwmeester, H.J., Hille, J., Poppinga, L. and Maijers, N.C. Amorpha-4,11-diene

synthase: cloning and functional expression of a key enzyme in the biosynthetic pathway of the
novel antimalarial drug artemisinin.

Planta

212 (2001) 460–465. [PMID:

11289612

]

2. Mercke, P., Bengtsson, M., Bouwmeester, H.J., Posthumus, M.A. and Brodelius, P.E. Molecular

cloning, expression, and characterization of amorpha-4,11-diene synthase, a key enzyme of
artemisinin biosynthesis in

Artemisia annua

Arch. Biochem. Biophys.

381 (2000) 173–180.

[PMID:

11032404

]

3. Bouwmeester, H.J., Wallaart, T.E., Janssen, M.H., van Loo, B., Jansen, B.J., Posthumus, M.A.,

Schmidt, C.O., De Kraker, J.W., König, W.A. and Franssen, M.C. Amorpha-4,11-diene synthase
catalyses the first probable step in artemisinin biosynthesis.

Phytochemistry

52 (1999) 843–854.

[PMID:

10626375

]

4. Chang, Y.J., Song, S.H., Park, S.H. and Kim, S.U. Amorpha-4,11-diene synthase of

Artemisia

annua

: cDNA isolation and bacterial expression of a terpene synthase involved in artemisinin

biosynthesis.

Arch. Biochem. Biophys.

383 (2000) 178–184. [PMID:

11185551

]

5. Martin, V.J., Pitera, D.J., Withers, S.T., Newman, J.D. and Keasling, J.D. Engineering a

mevalonate pathway in

Escherichia coli

for production of terpenoids.

Nat. Biotechnol.

21 (2003)

796–802. [PMID:

12778056

]

6. Picaud, S., Mercke, P., He, X., Sterner, O., Brodelius, M., Cane, D.E. and Brodelius, P.E.

Amorpha-4,11-diene synthase: Mechanism and stereochemistry of the enzymatic cyclization of
farnesyl diphosphate.

Arch. Biochem. Biophys.

448 (2006) 150–155. [PMID:

16143293

]

[EC 4.2.3.24 created 2006]

EC 4.2.3.25

Common name:

-linalool synthase

Reaction: geranyl diphosphate + H

O = (3

)-linalool + diphosphate

Glossary: (3

)-linalool = (3

)-3,7-dimethylocta-1,6-dien-3-ol

Other name(s): LIS; Lis; 3

-linalool synthase

Systematic name: geranyl-diphosphate diphosphate-lyase [(3

)-linalool-forming]

Comments: Requires Mn

or Mg

for activity. Neither (

)- nor (

)-linalyl diphosphate can act as substrate for

the enzyme from the flower

Clarkia breweri

[1]. Unlike many other monoterpene synthases, only a

single product, (3

)-linalool, is formed.

References: 1. Pichersky, E., Lewinsohn, E. and Croteau, R. Purification and characterization of

-linalool

synthase, an enzyme involved in the production of floral scent in

Clarkia breweri

Arch. Biochem.

Biophys.

316 (1995) 803–807. [PMID:

7864636

]

2. Lücker, J., Bouwmeester, H.J., Schwab, W., Blaas, J., van der Plas, L.H. and Verhoeven, H.A.

Expression of

Clarkia

-linalool synthase in transgenic petunia plants results in the accumulation

-linalyl-β-

-glucopyranoside.

Plant J.

27 (2001) 315–324. [PMID:

11532177

]

3. Dudareva, N., Cseke, L., Blanc, V.M. and Pichersky, E. Evolution of floral scent in

Clarkia

: novel

patterns of

-linalool synthase gene expression in the

C. breweri

flower.

Plant Cell

8 (1996)

1137–1148. [PMID:

8768373

]

[EC 4.2.3.25 created 2006]

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EC 4.2.3.26

Common name:

-linalool synthase

Reaction: geranyl diphosphate + H

O = (3

)-linalool + diphosphate

Glossary: (3

)-linalool = (3

)-3,7-dimethylocta-1,6-dien-3-ol

Other name(s): (3

)-linalool synthase; (-)-3

-linalool synthase

Systematic name: geranyl-diphosphate diphosphate-lyase [(3

)-linalool-forming]

Comments: Geranyl diphosphate cannot be replaced by isopentenyl diphosphate, dimethylallyl diphosphate,

farnesyl diphosphate or geranylgeranyl diphosphate as substrate [1]. Requires Mg

or Mn

for

activity. Unlike many other monoterpene synthases, only a single product, (3

)-linalool, is formed.

References: 1. Jia, J.W., Crock, J., Lu, S., Croteau, R. and Chen, X.Y. (3

)-Linalool synthase from

Artemisia

annua

L.: cDNA isolation, characterization, and wound induction.

Arch. Biochem. Biophys.

372

(1999) 143–149. [PMID:

10562427

]

2. Crowell, A.L., Williams, D.C., Davis, E.M., Wildung, M.R. and Croteau, R. Molecular cloning and

characterization of a new linalool synthase.

Arch. Biochem. Biophys.

405 (2002) 112–121.

[PMID:

12176064

]

[EC 4.2.3.26 created 2006]

EC 4.4.1.24

Common name: sulfolactate sulfo-lyase

Reaction: 3-sulfolactate = pyruvate + bisulfite

Other name(s): Suy; SuyAB

Systematic name: 3-sulfolactate bisulfite-lyase

Comments: Requires iron(II). This inducible enzyme from

Paracoccus pantotrophus

NKNCYSA forms part of

the cysteate-degradation pathway.

-Cysteate [(2

)-2-amino-3-sulfopropanoate] serves as a sole

source of carbon and energy for the aerobic growth of bacteria, as an electron acceptor for several
sulfate-reducing bacteria, as an electron donor for some nitrate-reducing bacteria and as a
substrate for a fermentation in a sulfate-reducing bacterium.

References: 1. Rein, U., Gueta, R., Denger, K., Ruff, J., Hollemeyer, K. and Cook, A.M. Dissimilation of cysteate

via 3-sulfolactate sulfo-lyase and a sulfate exporter in

Paracoccus pantotrophus

NKNCYSA.

Microbiology

151 (2005) 737–747. [PMID:

15758220

]

[EC 4.4.1.24 created 2006]

EC 4.4.1.25

Common name:

-cysteate sulfo-lyase

Reaction:

-cysteate + H

O = pyruvate + bisulfite + NH

Glossary:

-cysteate = (2

)-2-amino-3-sulfopropanoate

Other name(s):

-cysteate sulfo-lyase (deaminating); CuyA

Systematic name:

-cysteate bisulfite-lyase (deaminating)

Comments: A pyridoxal-phosphate protein.

-Cysteine can also act as a substrate, but more slowly. It is

converted into pyruvate, sulfide and NH

. This inducible enzyme from the marine bacterium

Silicibacter pomeroyi

DSS-3 forms part of the cysteate-degradation pathway.

References: 1. Denger, K., Smits, T.H.M. and Cook, A.M.

-Cysteate sulpho-lyase, a widespread pyridoxal 5′-

phosphate-coupled desulphonative enzyme purified from

Silicibacter pomeroyi

DSS-3(T).

Biochem. J.

394 (2006) 657–664. [PMID:

16302849

]

[EC 4.4.1.25 created 2006]

EC 5.3.3.14

Common name:

trans

-2-decenoyl-[acyl-carrier protein] isomerase

Reaction:

trans

-dec-2-enoyl-[acyl-carrier-protein] =

cis

-dec-3-enoyl-[acyl-carrier-protein]

Other name(s): β-hydroxydecanoyl thioester dehydrase;

trans

-2-

cis

-3-decenoyl-ACP isomerase;

trans

-2,

cis

-3-

decenoyl-ACP isomerase;

trans

-2-decenoyl-ACP isomerase; FabM

06/27/2006 05:11 PM

The Enzyme Database: New Enzymes

Page 46 of 48

http://www.enzyme-database.org/newenz.php?sp=off

Systematic name: decenoyl-[acyl-carrier-protein] Δ

trans

-Δ

cis

-isomerase

Comments: While the enzyme from

Escherichia coli

is highly specific for the 10-carbon enoyl-ACP, the enzyme

from

Streptococcus pneumoniae

can also use the 12-carbon enoyl-ACP as substrate in vitro but not

14- or 16-carbon enoyl-ACPs [3]. ACP can be replaced by either CoA or

-acetylcysteamine

thioesters. The

cis

-3-enoyl product is required to form unsaturated fatty acids, such as palmitoleic

acid and

cis

-vaccenic acid, in dissociated (or type II) fatty-acid biosynthesis.

References: 1. Brock, D.J.H., Kass, L.R. and Bloch, K. β-Hydroxydecanoyl thioester dehydrase. II. Mode of

action.

J. Biol. Chem.

242 (1967) 4432–4440. [PMID:

4863740

]

2. Bloch, K. Enzymatic synthesis of monounsaturated fatty acids.

Acc. Chem. Res.

2 (1969) 193–

202.

3. Marrakchi, H., Choi, K.H. and Rock, C.O. A new mechanism for anaerobic unsaturated fatty acid

formation in

Streptococcus pneumoniae

J. Biol. Chem.

277 (2002) 44809–44816. [PMID:

12237320

]

4. Cronan, J.E., Jr. and Rock, C.O. Biosynthesis of membrane lipids. In: Neidhardt, F.C. (Ed.),

Escherichia coli and Salmonella: Cellular and Molecular Biology

, 2nd edn, vol. 1, ASM Press,

Washington, DC, 1996, pp. 612–636.

[EC 5.3.3.14 created 2006]

EC 5.4.99.18

Common name: 5-(carboxyamino)imidazole ribonucleotide mutase

Reaction: 5-carboxyamino-1-(5-phospho-

-ribosyl)imidazole = 5-amino-1-(5-phospho-

-ribosyl)imidazole-4-

carboxylate
For diagram of the late stages of purine biosynthesis,

click here

Other name(s):

-CAIR mutase; PurE;

-carboxyaminoimidazole ribonucleotide mutase; class I PurE

Systematic name: 5-carboxyamino-1-(5-phospho-

-ribosyl)imidazole carboxymutase

Comments: In eubacteria, fungi and plants, this enzyme, along with

EC 6.3.4.18

, 5-(carboxyamino)imidazole

ribonucleotide synthase, is required to carry out the single reaction catalysed by

EC 4.1.1.21

phosphoribosylaminoimidazole carboxylase, in vertebrates [6]. In the absence of

EC 6.3.2.6

phosphoribosylaminoimidazolesuccinocarboxamide synthase, the reaction is reversible [3]. The
substrate is readily converted into 5-amino-1-(5-phospho-

-ribosyl)imidazole by non-enzymic

decarboxylation [3].

References: 1. Meyer, E., Leonard, N.J., Bhat, B., Stubbe, J. and Smith, J.M. Purification and characterization of

the

purE

purK

, and

purC

gene products: identification of a previously unrecognized energy

requirement in the purine biosynthetic pathway.

Biochemistry

31 (1992) 5022–5032. [PMID:

1534690

]

2. Mueller, E.J., Meyer, E., Rudolph, J., Davisson, V.J. and Stubbe, J.

-Carboxyaminoimidazole

ribonucleotide: evidence for a new intermediate and two new enzymatic activities in the de novo
purine biosynthetic pathway of

Escherichia coli

Biochemistry

33 (1994) 2269–2278. [PMID:

8117684

]

3. Meyer, E., Kappock, T.J., Osuji, C. and Stubbe, J. Evidence for the direct transfer of the

carboxylate of

-carboxyaminoimidazole ribonucleotide (

-CAIR) to generate 4-carboxy-5-

aminoimidazole ribonucleotide catalyzed by

Escherichia coli

PurE, an

-CAIR mutase.

Biochemistry

38 (1999) 3012–3018. [PMID:

10074353

]

4. Mathews, I.I., Kappock, T.J., Stubbe, J. and Ealick, S.E. Crystal structure of

Escherichia coli

PurE, an unusual mutase in the purine biosynthetic pathway.

Structure

7 (1999) 1395–1406.

[PMID:

10574791

]

5. Firestine, S.M., Poon, S.W., Mueller, E.J., Stubbe, J. and Davisson, V.J. Reactions catalyzed by

5-aminoimidazole ribonucleotide carboxylases from

Escherichia coli

and

Gallus gallus

: a case

for divergent catalytic mechanisms.

Biochemistry

33 (1994) 11927–11934. [PMID:

7918411

]

6. Firestine, S.M., Misialek, S., Toffaletti, D.L., Klem, T.J., Perfect, J.R. and Davisson, V.J.

Biochemical role of the

Cryptococcus neoformans

ADE2 protein in fungal de novo purine

biosynthesis.

Arch. Biochem. Biophys.

351 (1998) 123–134. [PMID:

9500840

]

[EC 5.4.99.18 created 2006]

*EC 6.3.2.6

Common name: phosphoribosylaminoimidazolesuccinocarboxamide synthase

Reaction: ATP + 5-amino-1-(5-phospho-

-ribosyl)imidazole-4-carboxylate +

-aspartate = ADP + phosphate

+ (

)-2-[5-amino-1-(5-phospho-

-ribosyl)imidazole-4-carboxamido]succinate

For diagram of the late stages of purine biosynthesis,

click here

06/27/2006 05:11 PM

The Enzyme Database: New Enzymes

Page 47 of 48

http://www.enzyme-database.org/newenz.php?sp=off

Other name(s): phosphoribosylaminoimidazole-succinocarboxamide synthetase; PurC; SAICAR synthetase; 4-(

succinocarboxamide)-5-aminoimidazole synthetase; 4-[(

-succinylamino)carbonyl]-5-

aminoimidazole ribonucleotide synthetase; SAICARs;
phosphoribosylaminoimidazolesuccinocarboxamide synthetase; 5-aminoimidazole-4-

succinocarboxamide ribonucleotide synthetase

Systematic name: 5-amino-1-(5-phospho-

-ribosyl)imidazole-4-carboxylate:

-aspartate ligase (ADP-forming)

Comments: Forms part of the purine biosynthesis pathway.

Links to other databases:

BRENDA

ERGO

EXPASY

IUBMB

KEGG

PDB

, CAS registry number: 9023-67-0

References: 1. Lukens, L.N. and Buchanan, J.M. Biosynthesis of purines. XXIV. The enzymatic synthesis of 5-

amino-1-ribosyl-4-imidazolecarboxylic acid 5′-phosphate from 5-amino-1-ribosylimidazole 5′-
phosphate and carbon dioxide.

J. Biol. Chem.

234 (1959) 1799–1805. [PMID:

13672967

]

2. Parker, J. Identification of the

purC

gene product of

Escherichia coli

J. Bacteriol.

157 (1984)

712–717. [PMID:

6365889

]

3. Ebbole, D.J. and Zalkin, H. Cloning and characterization of a 12-gene cluster from

Bacillus

subtilis

encoding nine enzymes for de novo purine nucleotide synthesis.

J. Biol. Chem.

262

(1987) 8274–8287. [PMID:

3036807

]

4. Chen, Z.D., Dixon, J.E. and Zalkin, H. Cloning of a chicken liver cDNA encoding 5-

aminoimidazole ribonucleotide carboxylase and 5-aminoimidazole-4-

-succinocarboxamide

ribonucleotide synthetase by functional complementation of

Escherichia coli

pur

mutants.

Proc.

Natl. Acad. Sci. USA

87 (1990) 3097–3101. [PMID:

1691501

]

5. O'Donnell, A.F., Tiong, S., Nash, D. and Clark, D.V. The

Drosophila melanogaster

ade5

gene

encodes a bifunctional enzyme for two steps in the de novo purine synthesis pathway.

Genetics

154 (2000) 1239–1253. [PMID:

10757766

]

6. Nelson, S.W., Binkowski, D.J., Honzatko, R.B. and Fromm, H.J. Mechanism of action of

Escherichia coli

phosphoribosylaminoimidazolesuccinocarboxamide synthetase.

Biochemistry

(2005) 766–774. [PMID:

15641804

]

[EC 6.3.2.6 created 1961, modified 2000, modified 2006]

*EC 6.3.2.27

Common name: aerobactin synthase

Reaction: 4 ATP + citrate + 2 6-

-acetyl-6-

-hydroxy-

-lysine + 2 H

O = 4 ADP + 4 phosphate + aerobactin

For diagram of aerobactin biosynthesis,

click here

Other name(s): citrate:

-acetyl-

-hydroxy-

-lysine ligase (ADP-forming)

Systematic name: citrate:6-

-acetyl-6-

-hydroxy-

-lysine ligase (ADP-forming)

Comments: Requires Mg

. Aerobactin is one of a group of high-affinity iron chelators known as siderophores

and is produced under conditions of iron deprivation [5]. It is a dihydroxamate comprising two
molecules of 6-

-acetyl-6-

-hydroxylysine and one molecule of citric acid. This is the last of the

three enzymes involved in its synthesis, the others being

EC 1.14.13.59

-lysine 6-

monooxygenase (NADPH) and

EC 2.3.1.102

-hydroxylysine

-acetyltransferase [3].

Links to other databases:

BRENDA

ERGO

EXPASY

IUBMB

KEGG

, CAS registry number: 94047-30-0

References: 1. Appanna, D.L., Grundy, B.J., Szczepan, E.W. and Viswanatha, T. Aerobactin synthesis in a cell-

free system of

Aerobacter aerogenes

62-1.

Biochim. Biophys. Acta

801 (1984) 437–443.

2. Gibson, F. and Magrath, D.I. The isolation and characterization of a hydroxamic acid

(aerobactin) formed by

Aerobacter aerogenes

62-I.

Biochim. Biophys. Acta

192 (1969) 175–184.

[PMID:

4313071

]

3. Maurer, P.J. and Miller, M. Microbial iron chelators: total synthesis of aerobactin and its

constituent amino acid,

-acetyl-

-hydroxylysine.

J. Am. Chem. Soc.

104 (1982) 3096–3101.

4. de Lorenzo, V., Bindereif, A., Paw, B.H. and Neilands, J.B. Aerobactin biosynthesis and transport

genes of plasmid ColV-K30 in

Escherichia coli

K-12.

J. Bacteriol.

165 (1986) 570–578. [PMID:

2935523

]

5. Challis, G.L. A widely distributed bacterial pathway for siderophore biosynthesis independent of

nonribosomal peptide synthetases.

ChemBioChem

6 (2005) 601–611. [PMID:

15719346

]

[EC 6.3.2.27 created 2002, modified 2006]

EC 6.3.4.18

Common name: 5-(carboxyamino)imidazole ribonucleotide synthase

Reaction: ATP + 5-amino-1-(5-phospho-

-ribosyl)imidazole + HCO

= ADP + phosphate + 5-carboxyamino-

1-(5-phospho-

-ribosyl)imidazole

06/27/2006 05:11 PM

The Enzyme Database: New Enzymes

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For diagram of the late stages of purine biosynthesis,

click here

Other name(s):

-CAIR synthetase;

-carboxyaminoimidazole ribonucleotide synthetase; PurK

Systematic name: 5-amino-1-(5-phospho-

-ribosyl)imidazole:carbon-dioxide ligase (ADP-forming)

Comments: In

Escherichia coli

, this enzyme, along with

EC 5.4.99.18

, 5-(carboxyamino)imidazole

ribonucleotide mutase, is required to carry out the single reaction catalysed by

EC 4.1.1.21

phosphoribosylaminoimidazole carboxylase, in vertebrates. Belongs to the ATP grasp protein
superfamily [3]. Carboxyphosphate is the putative acyl phosphate intermediate. Involved in the late
stages of purine biosynthesis.

References: 1. Meyer, E., Leonard, N.J., Bhat, B., Stubbe, J. and Smith, J.M. Purification and characterization of

the

purE

purK

, and

purC

gene products: identification of a previously unrecognized energy

requirement in the purine biosynthetic pathway.

Biochemistry

31 (1992) 5022–5032. [PMID:

1534690

]

2. Mueller, E.J., Meyer, E., Rudolph, J., Davisson, V.J. and Stubbe, J.

-Carboxyaminoimidazole

ribonucleotide: evidence for a new intermediate and two new enzymatic activities in the de novo
purine biosynthetic pathway of

Escherichia coli

Biochemistry

33 (1994) 2269–2278. [PMID:

8117684

]

3. Thoden, J.B., Kappock, T.J., Stubbe, J. and Holden, H.M. Three-dimensional structure of

carboxyaminoimidazole ribonucleotide synthetase: a member of the ATP grasp protein
superfamily.

Biochemistry

38 (1999) 15480–15492. [PMID:

10569930

]

[EC 6.3.4.18 created 2006]