An asterisk before 'EC' indicates that this is an amendment to an existing enzyme rather than a new enzyme entry.
See also entries in separate files for EC 1, EC 2 and EC 4 to EC 6.
Common name: lipid-phosphate phosphatase
Reaction: (9S,10S)-10-hydroxy-9-(phosphonooxy)octadecanoate + H2O = (9S,10S)-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: (9S,10S)-10-hydroxy-9-(phosphonooxy)octadecanoate phosphohydrolase
Comments: Requires Mg2+ 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].
Links to other databases: BRENDA, ERGO, EXPASY, KEGG, CAS registry number:
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. 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]
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 (Mg2+, Mn2+ or Co2+). 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].
Links to other databases: BRENDA, ERGO, EXPASY, KEGG, CAS registry number:
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 Escherichia coli rnd gene encoding RNase D. J. Bacteriol. 170 (1988) 522-527. [PMID: 2828310]
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, KEGG, PDB, CAS registry number: 78413-14-6
References:
1. Crouch, R.J. Ribonuclease 3 does not degrade deoxyribonucleic acid-ribonucleic acid hybrids. J. 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. (Ed.), Control of Messenger RNA Stability, vol. , 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]
Common name: β-agarase
Reaction: Hydrolysis of 1,4-β-D-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-L-galactopyranosyl-(1→3)-D-galactose
agarobiose = β-D-galactopyranosyl-(1→4)-3,6-anhydro-L-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, 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]
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. 59 (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]
Common name: κ-carrageenase
Reaction: Endohydrolysis of 1,4-β-D-linkages between D-galactose 4-sulfate and 3,6-anhydro-D-galactose in κ-carrageenans
For diagram, 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-O-sulfo-α-D-galactopyranosyl-(1→3)-4-O-sulfo-D-galactose
ι-carrabiose = 4-O-sulfo- β-D-galactopyranosyl-(1→4)-3,6-anhydro-2-O-sulfo-D-galactose
Other name(s): κ-carrageenan 4-β-D-glycanohydrolase
Systematic name: κ-carrageenan 4-β-D-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, 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]
Common name: ι-carrageenase
Reaction: Endohydrolysis of 1,4-β-D-linkages between D-galactose 4-sulfate and 3,6-anhydro-D-galactose-2-sulfate in ι-carrageenans
For diagram, 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-O-sulfo-α-D-galactopyranosyl-(1→3)-4-O-sulfo-D-galactose
ι-carrabiose = 4-O-sulfo-β-D-galactopyranosyl-(1→4)-3,6-anhydro-2-O-sulfo-D-galactose
Systematic name: ι-carrageenan 4-β-D-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 O-2 of the 3,6-anhydro-D-galactose residues, in addition to that present in the κ-compound on O-4 of the D-galactose residues.
Links to other databases: BRENDA, ERGO, EXPASY, KEGG, CAS registry number:
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]
Common name: α-agarase
Reaction: Endohydrolysis of 1,3-α-L-galactosidic linkages in agarose, yielding agarotetraose as the major 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-L-galactopyranosyl-(1→3)-D-galactose
agarobiose = β-D-galactopyranosyl-(1→4)-3,6-anhydro-L-galactose
Other name(s): agarase (ambiguous); agaraseA33
Systematic name: agarose 3-glycanohydrolase
Comments: Requires Ca2+. 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.
Links to other databases: BRENDA, ERGO, EXPASY, KEGG, CAS registry number:
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 (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]
Common name: α-neoagaro-oligosaccharide hydrolase
Reaction: Hydrolysis of the 1,3-α-L-galactosidic linkages of neoagaro-oligosaccharides that are smaller than a hexamer, yielding 3,6-anhydro-L-galactose and D-galactose
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:
neoagarobiose = 3,6-anhydro-α-L-galactopyranosyl-(1→3)-D-galactose
agarobiose = β-D-galactopyranosyl-(1→4)-3,6-anhydro-L-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-L-galactose and agaropentaose, which is further hydrolysed to agarobiose and agarotriose. With neoagarotetraose as substrate, the products are predominantly agarotriose and 3,6-anhydro-L-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-L-galactose and D-galactose.
Links to other databases: BRENDA, ERGO, EXPASY, KEGG, CAS registry number:
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 3.2.1.160 Deleted entry: xyloglucan-specific exo-β-1,4-glucanase. The enzyme was shown to be identical to EC 3.2.1.155, xyloglucan-specific exo-β-1,4-glucanase, during the public-review process so was withdrawn before being made official. (EC 3.2.1.160 created 2006, deleted 2006)]
Common name: β-apiosyl-β-glucosidase
Reaction: 7-[β-D-apiofuranosyl-(1→6)-β-D-glucopyranosyloxy]isoflavonoid + H2O = a 7-hydroxyisoflavonoid + β-D-apiofuranosyl-(1→6)-D-glucose
Other name(s): isoflavonoid-7-O-β[D-apiosyl-(1→6)-β-D-glucoside] disaccharidase; isoflavonoid 7-O-β-apiosyl-glucoside β-glucosidase; furcatin hydrolase
Systematic name: 7-[β-D-apiofuranosyl-(1→6)-β-D-glucopyranosyloxy]isoflavonoid β-D-apiofuranosyl-(1→6)-D-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-O-β-D-apiofuranosyl-(1→6)-β-D-glucopyranoside and 7-hydroxy-2',4',5',6-tetramethoxy-7-O-β-D-apiofuranosyl-(1→6)-β-D-glucopyranoside (dalnigrein 7-O-β-D-apiofuranosyl-(1→6)-β-D-glucopyranoside) although it can also remove a single glucose residue from isoflavonoid 7-O-glucosides [2]. Daidzin and genistin are also substrates.
Links to other databases: BRENDA, ERGO, EXPASY, KEGG, CAS registry number:
References:
1. Hosel, W. and Barz, W. β-Glucosidases from Cicer arietinum L. Purification and Properties of isoflavone-7-O-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-O-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 3.3.2.3 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)]
Common name: leukotriene-A4 hydrolase
Reaction: (7E,9E,11Z,14Z)-(5S,6S)-5,6-epoxyicosa-7,9,11,14-tetraenoate + H2O = (6Z,8E,10E,14Z)-(5S,12R)-5,12-dihydroxyicosa-6,8,10,14-tetraenoate
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 3.2.2.10, 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) [3].
Links to other databases: BRENDA, ERGO, EXPASY, 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 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]
Common name: hepoxilin-epoxide hydrolase
Reaction: (5Z,9E,14Z)-(8ξ,11R,12S)-11,12-epoxy-8-hydroxyicosa-5,9,14-trienoate + H2O = (5Z,9E,14Z)-(8ξ,11ξ,12S)-8,11,12-trihydroxyicosa-5,9,14-trienoate
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, ERGO, EXPASY, KEGG, 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]
Common 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, ERGO, EXPASY, KEGG, 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]
Common 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, ERGO, EXPASY, KEGG, CAS registry number:
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]
Common name: cholesterol-5,6-oxide hydrolase
Reaction: (1) 5,6α-epoxy-5α-cholestan-3β-ol + H2O = cholestane-3β-5α,6β-triol
(2) 5,6β-epoxy-5β-cholestan-3β-ol + H2O = cholestane-3β-5α,6β-triol
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, ERGO, EXPASY, KEGG, 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 3.4.21.87 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)]
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: BRENDA, ERGO, EXPASY, KEGG, 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, vol. , 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]
Common name: γ-glutamyl-γ-aminobutyrate hydrolase
Reaction: 4-(glutamylamino)butanoate + H2O = 4-aminobutanoate + L-glutamate
Other name(s): γ-glutamyl-GABA hydrolase; PuuD; YcjL
Systematic name: 4-(glutamylamino)butanoate amidohydrolase
Comments: Forms part of a novel putrescine-utilizing pathway in Escherichia coli, in which it has been hypothesized that putrescine is first glutamylated to form γ-glutamylputrescine, which is oxidized to 4-(glutamylamino)butanal and then to 4-(glutamylamino)butanoate. The enzyme can also catalyse the reactions of EC 3.5.1.35 (D-glutaminase) and EC 3.5.1.65 (theanine hydrolase).
Links to other databases: BRENDA, ERGO, EXPASY, KEGG, CAS registry number:
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. J. Biol. Chem. 280 (2005) 4602-4608. [PMID: 15590624]
Common name: N-malonylurea hydrolase
Reaction: 3-oxo-3-ureidopropanoate + H2O = malonate + urea
For diagram, 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 EC 1.17.99.4 (uracil/thymine dehydrogenase) and EC 3.5.2.1 (barbiturase).
Links to other databases: BRENDA, ERGO, EXPASY, KEGG, CAS registry number:
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]
Common name: succinylglutamate desuccinylase
Reaction: N-succinyl-L-glutamate + H2O = succinate + L-glutamate
For diagram, click here
Other name(s): N2-succinylglutamate desuccinylase; SGDS; AstE
Systematic name: N-succinyl-L-glutamate amidohydrolase
Comments: Requires Co2+ for maximal activity [1]. N2-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 N-succinyltransferase), EC 3.5.3.23 (N-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).
Links to other databases: BRENDA, ERGO, EXPASY, KEGG, CAS registry number:
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. 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]
4. 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]
Common name: barbiturase
Reaction: barbiturate + H2O = 3-oxo-3-ureidopropanoate
For diagram, click here
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 (N-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, 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]
Common name: N-succinylarginine dihydrolase
Reaction: N2-succinyl-L-arginine + 2 H2O = N2-succinyl-L-ornithine + 2 NH3 + CO2
For diagram, click here
Other name(s): N2-succinylarginine dihydrolase; arginine succinylhydrolase; SADH; AruB; AstB
Systematic name: N2-succinyl-L-arginine iminohydrolase (decarboxylating)
Comments: Arginine, N2-acetylarginine and N2-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 N-succinyltransferase), EC 3.5.3.23 (N-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).
Links to other databases: BRENDA, ERGO, EXPASY, KEGG, CAS registry number:
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 N-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]
Common name: Zn2+-exporting ATPase
Reaction: ATP + H2O + Zn2+in = ADP + phosphate + Zn2+out
Other name(s): Zn(II)-translocating P-type ATPase; P1B-type ATPase; AtHMA4
Systematic name: ATP phosphohydrolase (Zn2+-exporting)
Comments: A P-type ATPase that undergoes covalent phosphorylation during the transport cycle. This enzyme also exports Cd2+ and Pb2+.
Links to other databases: BRENDA, ERGO, EXPASY, KEGG, PDB, CAS registry number:
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 Arguello, J.M. Arabidopsis HMA2, a divalent heavy metal-transporting P(IB)-type ATPase, is involved in cytoplasmic Zn2+ homeostasis. Plant Physiol. 136 (2004) 3712-3723. [PMID: 15475410]
Common name: xenobiotic-transporting ATPase
Reaction: ATP + H2O + xenobioticin = ADP + phosphate + xenobioticout
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, KEGG CAS registry number:
References:
1. Bellamy, W.T. P-glycoproteins and multidrug resistance. Annu. Rev. Pharmac. Toxicol. 36 (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 Mr 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. (Ed.), 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 3.6.3.45 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)]