Enzyme Nomenclature

Continued from EC 3.2.2 and EC 3.2.3

EC 3.3

Acting on Ether Bonds

Sections

EC 3.3.1 Thioether and trialkylsulfonium hydrolases
EC 3.3.2 Ether Hydrolases


EC 3.3.1 Thioether and trialkylsulfonium hydrolases

Contents

EC 3.3.1.1 adenosylhomocysteinase
EC 3.3.1.2 adenosylmethionine hydrolase
EC 3.3.1.3 now EC 3.2.1.148 ribosylhomocysteinase


Entries

EC 3.3.1.1

Accepted name: adenosylhomocysteinase

Reaction: S-adenosyl-L-homocysteine + H2O = L-homocysteine + adenosine

For diagram click here.

Other name(s): S-adenosylhomocysteine synthase; S-adenosylhomocysteine hydrolase; adenosylhomocysteine hydrolase (ambiguous); S-adenosylhomocysteinase; SAHase; AdoHcyase

Systematic name: S-adenosyl-L-homocysteine hydrolase

Comments: The enzyme contains one tightly bound NAD+ per subunit. This appears to bring about a transient oxidation at C-3' of the 5'-deoxyadenosine residue, thus labilizing the thioether bond [2] (for mechanism click here), cf. EC 5.5.1.4, inositol-3-phosphate synthase.

Links to other databases: BRENDA, EXPASY, GTD, KEGG, Metacyc, PDB, CAS registry number: 9025-54-1

References:

1. de la Haba, G. and Cantoni, G.L. The enzymatic synthesis of S-adenosyl-L-homocysteine from adenosine and homocysteine. J. Biol. Chem. 234 (1959) 603-608. [PMID: 13641268]

2. Palmer, J.L. and Abeles, R.H. The mechanism of action of S-adenosylhomocysteinase. J. Biol. Chem. 254 (1979) 1217-1226. [PMID: 762125]

[EC 3.3.1.1 created 1961, modified 2004]

EC 3.3.1.2

Accepted name: adenosylmethionine hydrolase

Reaction: S-adenosyl-L-methionine + H2O = L-homoserine + S-methyl-5'-thioadenosine

Glossary: S-methyl-L-methionine sulfonium salt = (S)-3-amino-3-carboxypropyldi(methyl)sulfonium salt

Other name(s): S-adenosylmethionine cleaving enzyme; methylmethionine-sulfonium-salt hydrolase; adenosylmethionine lyase

Systematic name: S-adenosyl-L-methionine hydrolase

Comments: Also hydrolyses S-methyl-L-methionine sulfonium salt to dimethyl sulfide and homoserine.

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number: 37288-62-3

References:

1. Mazelis, M., Levin, B. and Mallinson, N. Decomposition of methyl methionine sulfonium salts by a bacterial enzyme. Biochim. Biophys. Acta 105 (1965) 106-114. [PMID: 5849106]

[EC 3.3.1.2 created 1972, modified 1976]

[EC 3.3.1.3 Transferred entry: now EC 3.2.1.148 ribosylhomocysteinase (EC 3.3.1.3 created 1972, deleted 2001)]


EC 3.3.2 Ether Hydrolases

Contents

EC 3.3.2.1 isochorismatase
EC 3.3.2.2 lysoplasmalogenase
EC 3.3.2.3 now EC 3.3.2.9 and EC 3.3.2.10
EC 3.3.2.4 trans-epoxysuccinate hydrolase
EC 3.3.2.5 transferred now covered by EC 3.3.2.2
EC 3.3.2.6 leukotriene-A4 hydrolase
EC 3.3.2.7 hepoxilin-epoxide hydrolase
EC 3.3.2.8 limonene-1,2-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 3.3.2.12 oxepin-CoA hydrolase
EC 3.3.2.13 chorismatase
EC 3.3.2.14 2,4-dinitroanisole O-demethylase
EC 3.3.2.15 trans-2,3-dihydro-3-hydroxyanthranilic acid synthase

Entries

EC 3.3.2.1

Accepted name: isochorismatase

Reaction: isochorismate + H2O = (2S,3S)-2,3-dihydroxy-2,3-dihydrobenzoate + pyruvate

For diagram of reaction, click here.

Glossary: isochorismate = (5S,6S)-5-[(1-carboxyethenyl)oxy]-6-hydroxycyclohexa-1,3-diene-1-carboxylate

Other name(s): 2,3-dihydro-2,3-dihydroxybenzoate synthase; 2,3-dihydroxy-2,3-dihydrobenzoate synthase; 2,3-dihydroxy-2,3-dihydrobenzoic synthase

Systematic name: isochorismate pyruvate-hydrolase

Comments: The enzyme is involved in the biosynthesis of several siderophores, such as 2,3-dihydroxybenzoylglycine, enterobactin, bacillibactin, and vibriobactin.

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, PDB, CAS registry number: 37288-64-5

References:

1. Young, I.G. and Gibson, F. Regulation of the enzymes involved in the biosynthesis of 2,3-dihydroxybenzoic acid in Aerobacter aerogenes and Escherichia coli. Biochim. Biophys. Acta 177 (1969) 401-411. [PMID: 4306838]

[EC 3.3.2.1 created 1972]

EC 3.3.2.2

Accepted name: lysoplasmalogenase

Reaction: (1) 1-(1-alkenyl)-sn-glycero-3-phosphocholine + H2O = an aldehyde + sn-glycero-3-phosphocholine
(2) 1-(1-alkenyl)-sn-glycero-3-phosphoethanolamine + H2O = an aldehyde + sn-glycero-3-phosphoethanolamine

Other name(s): alkenylglycerophosphocholine hydrolase; alkenylglycerophosphoethanolamine hydrolase; 1-(1-alkenyl)-sn-glycero-3-phosphocholine aldehydohydrolase

Systematic name: lysoplasmalogen aldehydohydrolase

Comments: Lysoplasmalogenase is specific for the sn-2-deacylated (lyso) form of plasmalogen and catalyses hydrolytic cleavage of the vinyl ether bond, releasing a fatty aldehyde and sn-glycero-3-phosphocholine or sn-glycero-3-phosphoethanolamine.

Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number: 37288-65-6

References:

1. Warner, H.R. and Lands, W.E.M. The metabolism of plasmalogen: enzymatic hydrolysis of the vinyl ether. J. Biol. Chem. 236 (1961) 2404-2409. [PMID: 13783189]

2. Ellingson, J.S. and Lands, W.E.M. Phospholipid reactivation of plasmalogen metabolism. Lipids 3 (1968) 111-120. [PMID: 17805898]

3. Gunawan, J. and Debuch, H. Liberation of free aldehyde from 1-(1-alkenyl)-sn-glycero-3-phosphoethanolamine (lysoplasmalogen) by rat liver microsomes. Hoppe-Seyler's Z. Physiol. Chem. 362 (1981) 445-452. [PMID: 7239443]

4. Arthur, G., Page, L., Mock, T. and Choy, P.C. The catabolism of plasmenylcholine in the guinea pig heart. Biochem. J. 236 (1986) 475-480. [PMID: 3753461]

5. Wu, L.C., Pfeiffer, D.R., Calhoon, E.A., Madiai, F., Marcucci, G., Liu, S. and Jurkowitz, M.S. Purification, identification, and cloning of lysoplasmalogenase, the enzyme that catalyzes hydrolysis of the vinyl ether bond of lysoplasmalogen. J. Biol. Chem. 286 (2011) 24916-24930. [PMID: 21515882]

[EC 3.3.2.2 created 1972, modified 1976, (EC 3.3.2.5 created 1984, incorporated 2016), modified 2016]

[EC 3.3.2.3 Transferred entry: epoxide hydrolase. Now known to comprise two enzymes, microsomal epoxide hydrolase (EC 3.3.2.9) and soluble epoxide hydrolase (EC 3.3.2.10). (EC 3.3.2.3 created 1978, modified 1999, deleted 2006)]

EC 3.3.2.4

Accepted name: trans-epoxysuccinate hydrolase

Reaction: trans-2,3-epoxysuccinate + H2O = meso-tartrate

Other name(s): trans-epoxysuccinate hydratase; tartrate epoxydase

Systematic name: trans-2,3-epoxysuccinate hydrolase

Comments: Acts on both optical isomers of the substrate. Formerly EC 4.2.1.37.

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number: 37290-73-6

References:

1. Allen, R.H. and Jakoby, W.B. Tartaric acid metabolism. IX. Synthesis with tartrate epoxidase. J. Biol. Chem. 244 (1969) 2078-2084. [PMID: 5782001]

[EC 3.3.2.4 created 1984]

[EC 3.3.2.5 Transferred entry: alkenylglycerophosphoethanolamine hydrolase, now included in EC 3.3.2.2, lysoplasmalogenase. (EC 3.3.2.5 created 1984, deleted 2016)]

EC 3.3.2.6

Accepted name: leukotriene-A4 hydrolase

Reaction: leukotriene A4 + H2O = leukotriene B4

Glossary: leukotriene A4 = (7E,9E,11Z,14Z)-(5S,6S)-5,6-epoxyicosa-7,9,11,14-tetraenoate
leukotriene B4 = (6Z,8E,10E,14Z)-(5S,12R)-5,12-dihydroxyicosa-6,8,10,14-tetraenoate

Other name(s): LTA4 hydrolase; LTA4H; leukotriene A4 hydrolase

Systematic name: (7E,9E,11Z,14Z)-(5S,6S)-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 A4 into leukotriene B4, unlike EC 3.3.2.10, soluble epoxide hydrolase, which converts leukotriene A4 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 A4 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) [5].

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, PDB, CAS registry number: 90119-07-6

References:

1. Evans, J.F., Dupuis, P. and Ford-Hutchinson, A.W. Purification and characterisation of leukotriene A4 hydrolase from rat neutrophils. Biochim. Biophys. Acta 840 (1985) 43-50. [PMID: 3995081]

2. Minami, M., Ohno, S., Kawasaki, H., Raadmark, O., Samuelsson, B., Jörnvall, H., Shimizu, T., Seyama, Y. and Suzuki, K. Molecular cloning of a cDNA coding for human leukotriene A4 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 Radmark, O. Leukotriene A4. 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-A4 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 A4 hydrolase in the human lung. Inactivation of the enzyme with leukotriene A4 isomers. J. Biol. Chem. 262 (1987) 10200-10205. [PMID: 3038871]

[EC 3.3.2.6 created 1989, modified 2006]

EC 3.3.2.7

Accepted name: hepoxilin-epoxide hydrolase

Reaction: hepoxilin A3 + H2O = trioxilin A3

Glossary: hepoxilin A3 = (5Z,9E,14Z)-(8ξ,11R,12S)-11,12-epoxy-8-hydroxyicosa-5,9,14-trienoate
trioxilin A3 = (5Z,9E,14Z)-(8ξ,11ξ,12S)-8,11,12-trihydroxyicosa-5,9,14-trienoate

Other name(s): hepoxilin epoxide hydrolase; hepoxylin hydrolase; hepoxilin A3 hydrolase

Systematic name: (5Z,9E,14Z)-(8ξ,11R,12S)-11,12-epoxy-8-hydroxyicosa-5,9,14-trienoate hydrolase

Comments: Converts hepoxilin A3 into trioxilin A3. Highly specific for the substrate, having only slight activity with other epoxides such as leukotriene A4 and styrene oxide [2]. Hepoxilin A3 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-A4 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, EXPASY, KEGG, Metacyc, CAS registry number: 122096-98-4

References:

1. Pace-Asciak, C.R. Formation and metabolism of hepoxilin A3 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. J. 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 3.3.2.8

Accepted name: limonene-1,2-epoxide hydrolase

Reaction: limonene-1,2-epoxide + H2O = limonene-1,2-diol

For diagram of reaction click here.

Glossary:
limonene = mentha-1,8-diene
limonene-1,2-epoxide = 1,2-epoxymenth-8-ene
limonene-1,2-diol = menth-8-ene-1,2-diol

Other name(s): limonene oxide hydrolase

Systematic name: limonene-1,2-epoxide hydrolase

Comment: Involved in the monoterpene degradation pathway of the actinomycete Rhodococcus erythropolis. Enzyme hydrolyses several alicyclic and 1-methyl-substituted epoxides, such as 1-methylcyclohexene oxide, indene oxide and cyclohexene oxide. It differs from the previously described epoxide hydrolases [EC 3.3.2.4 (trans-epoxysuccinate hydrolase), EC 3.3.2.6 (leukotriene-A4 hydrolase), EC 3.3.2.7 (hepoxilin-epoxide hydrolase), EC 3.3.2.9 (microsomal epoxide hydrolase) and EC 3.3.2.10 (soluble epoxide hydrolase)] as it is not inhibited by 2-bromo-4'-nitroacetophenone, diethyl dicarbonate, 4-fluorochalcone oxide or 1,10-phenanthroline.

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, PDB, UM-BBD, CAS registry number: 216503-88-7

References:

1. van der Werf, M.J., Overkamp, K.M. and de Bont, J.A.M. Limonene-1,2-epoxide hydrolase from Rhodococcus erythropolis DCL14 belongs to a novel class of epoxide hydrolases. J. Bacteriol. 180 (1998) 5052-5057. [PMID: 9748436]

2. Barbirato, F., Verdoes, J.C., de Bont, J.A.M. and van der Werf, M.J. The Rhodococcus erythropolis DCL14 limonene-1,2-epoxide hydrolase gene encodes an enzyme belonging to a novel class of epoxide hydrolases. FEBS Lett. 438 (1998) 293-296. [PMID: 9827564]

[EC 3.3.2.8 created 2001]

EC 3.3.2.9

Accepted name: microsomal epoxide hydrolase

Reaction: cis-stilbene oxide + H2O = (+)-(1R,2R)-1,2-diphenylethane-1,2-diol

Other name(s): epoxide hydratase (ambiguous); microsomal epoxide hydratase; epoxide hydrase; microsomal epoxide hydrase; arene-oxide hydratase (ambiguous); benzo[a]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[a]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-A4 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].

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, UM-BBD, CAS registry number:

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.

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

Accepted name: soluble epoxide hydrolase

Reaction: an epoxide + H2O = a glycol

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 A4, the substrate of EC 3.3.2.6, leukotriene-A4 hydrolase, but it forms 5,6-dihydroxy-7,9,11,14-eicosatetraenoic acid rather than leukotriene B4 as the product [9,10]. In vertebrates, five epoxide-hydrolase enzymes have been identified to date: EC 3.3.2.6 (leukotriene-A4 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].

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, PDB, CAS registry number: 9048-63-9

References:

1. Newman, J.W., Morisseau, C., Harris, T.R. and Hammock, B.D. The soluble epoxide hydrolase encoded by EPXH2 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., Durk, 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 Radmark, O. Leukotriene A4. 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 3.3.2.11

Accepted name: cholesterol-5,6-oxide hydrolase

Reaction: (1) 5,6α-epoxy-5α-cholestan-3β-ol + H2O = 5α-cholestane-3β,5α,6β-triol
(2) 5,6β-epoxy-5β-cholestan-3β-ol + H2O = 5α-cholestane-3β,5α,6β-triol

For diagram 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-A4 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, EXPASY, KEGG, Metacyc, CAS registry number:

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 3.3.2.12

Accepted name: oxepin-CoA hydrolase

Reaction: 2-oxepin-2(3H)-ylideneacetyl-CoA + H2O = 3-oxo-5,6-dehydrosuberyl-CoA semialdehyde

For diagram of reaction click here.

Glossary: oxepin-CoA = 2-oxepin-2(3H)-ylideneacetyl-CoA

Other name(s): paaZ (gene name)

Systematic name: 2-oxepin-2(3H)-ylideneacetyl-CoA hydrolase

Comments: The enzyme from Escherichia coli is a bifunctional fusion protein that also catalyses EC 1.17.1.7, 3-oxo-5,6-dehydrosuberyl-CoA semialdehyde dehydrogenase. Combined the two activities result in a two-step conversion of oxepin-CoA to 3-oxo-5,6-dehydrosuberyl-CoA, part of an aerobic phenylacetate degradation pathway [1,3,4]. The enzyme from Escherichia coli also exhibits enoyl-CoA hydratase activity utilizing crotonyl-CoA as a substrate [2].

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number:

References:

1. Ferrandez, A., Minambres, B., Garcia, B., Olivera, E.R., Luengo, J.M., Garcia, J.L. and Diaz, E. Catabolism of phenylacetic acid in Escherichia coli. Characterization of a new aerobic hybrid pathway. J. Biol. Chem. 273 (1998) 25974-25986. [PMID: 9748275]

2. Park, S.J. and Lee, S.Y. Identification and characterization of a new enoyl coenzyme A hydratase involved in biosynthesis of medium-chain-length polyhydroxyalkanoates in recombinant Escherichia coli. J. Bacteriol. 185 (2003) 5391-5397. [PMID: 12949091]

3. Ismail, W., El-Said Mohamed, M., Wanner, B.L., Datsenko, K.A., Eisenreich, W., Rohdich, F., Bacher, A. and Fuchs, G. Functional genomics by NMR spectroscopy. Phenylacetate catabolism in Escherichia coli. Eur. J. Biochem. 270 (2003) 3047-3054. [PMID: 12846838]

4. Teufel, R., Mascaraque, V., Ismail, W., Voss, M., Perera, J., Eisenreich, W., Haehnel, W. and Fuchs, G. Bacterial phenylalanine and phenylacetate catabolic pathway revealed. Proc. Natl. Acad. Sci. USA 107 (2010) 14390-14395. [PMID: 20660314]

[EC 3.3.2.12 created 2011 as EC 3.7.1.16, transferred 2013 to EC 3.3.2.13]

EC 3.3.2.13

Accepted name: chorismatase

Reaction: chorismate + H2O = (4R,5R)-4,5-dihydroxycyclohexa-1(6),2-diene-1-carboxylate + pyruvate

For diagram of reaction, click here

Glossary: chorismate = (3R,4R)-3-[(1-carboxyethenyl)oxy]-4-hydroxycyclohexa-1,5-diene-1-carboxylate

Other name(s): chorismate/3,4-dihydroxycyclohexa-1,5-dienoate synthase; fkbO (gene name); rapK (gene name)

Systematic name: chorismate pyruvate-hydrolase

Comments: The enzyme found in several bacterial species is involved in the biosynthesis of macrocyclic polyketides.

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number:

References:

1. Andexer, J.N., Kendrew, S.G., Nur-e-Alam, M., Lazos, O., Foster, T.A., Zimmermann, A.S., Warneck, T.D., Suthar, D., Coates, N.J., Koehn, F.E., Skotnicki, J.S., Carter, G.T., Gregory, M.A., Martin, C.J., Moss, S.J., Leadlay, P.F. and Wilkinson, B. Biosynthesis of the immunosuppressants FK506, FK520, and rapamycin involves a previously undescribed family of enzymes acting on chorismate. Proc. Natl. Acad. Sci. USA 108 (2011) 4776-4781. [PMID: 21383123]

2. Juneja, P., Hubrich, F., Diederichs, K., Welte, W. and Andexer, J.N. Mechanistic implications for the chorismatase FkbO based on the crystal structure. J. Mol. Biol. (2013) . [PMID: 24036425]

[EC 3.3.2.13 created 2013]

EC 3.3.2.14

Accepted name: 2,4-dinitroanisole O-demethylase

Reaction: 2,4-dinitroanisole + H2O = methanol + 2,4-dinitrophenol

Glossary: 2,4-dinitroanisole = 1-methoxy-2,4-dinitrobenzene

Other name(s): 2,4-dinitroanisole ether hydrolase; dnhA (gene name); dnhB (gene name); DNAN demethylase

Systematic name: 2,4-dinitroanisole methanol hydrolase

Comments: The enzyme, characterized from the bacterium Nocardioides sp. JS1661, is involved in the degradation of 2,4-dinitroanisole. Unlike other known O-demethylases, such as EC 1.14.99.15, 4-methoxybenzoate monooxygenase (O-demethylating), or EC 1.14.11.32, codeine 3-O-demethylase, it does not require oxygen or electron donors, and produces methanol rather than formaldehyde.

References:

1. Fida, T.T., Palamuru, S., Pandey, G. and Spain, J.C. Aerobic biodegradation of 2,4-dinitroanisole by Nocardioides sp. strain JS1661. Appl. Environ. Microbiol. 80 (2014) 7725-7731. [PMID: 25281383]

[EC 3.3.2.14 created 2015]

EC 3.3.2.15

Accepted name: trans-2,3-dihydro-3-hydroxyanthranilic acid synthase

Reaction: (2S)-2-amino-4-deoxychorismate + H2O = (5S,6S)-6-amino-5-hydroxycyclohexa-1,3-diene-1-carboxylate + pyruvate

Glossary: (5S,6S)-6-amino-5-hydroxycyclohexa-1,3-diene-1-carboxylate = trans-2,3-dihydro-3-hydroxyanthranilate

Other name(s): isochorismatase (ambiguous); phzD (gene name)

Systematic name: (2S)-2-amino-4-deoxychorismate pyruvate-hydrolase

Comments: Isolated from the bacterium Pseudomonas aeruginosa. Involved in phenazine biosynthesis.

Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:

References:

1. Mavrodi, D.V., Bonsall, R.F., Delaney, S.M., Soule, M.J., Phillips, G. and Thomashow, L.S. Functional analysis of genes for biosynthesis of pyocyanin and phenazine-1-carboxamide from Pseudomonas aeruginosa PAO1. J. Bacteriol. 183 (2001) 6454-6465. [PMID: 11591691]

2. Parsons, J.F., Calabrese, K., Eisenstein, E. and Ladner, J.E. Structure and mechanism of Pseudomonas aeruginosa PhzD, an isochorismatase from the phenazine biosynthetic pathway. Biochemistry 42 (2003) 5684-5693. [PMID: 12741825]

[EC 3.3.2.15 created 2016]


Continued with EC 3.4
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