Xaa bond to release a C-terminal amino acidContinued from EC 3.4.11 to EC 3.4.15.
EC 3.4.16 Serine-type carboxypeptidases
EC 3.4.17 Metallocarboxypeptidases
EC 3.4.18 Cysteine-type carboxypeptidases
EC 3.4.19 Omega peptidases
Contents
EC 3.4.16.1 deleted, included in EC 3.4.16.5, EC 3.4.16.6
EC 3.4.16.2 lysosomal Pro-Xaa carboxypeptidase
EC 3.4.16.3 deleted, included in EC 3.4.16.5
EC 3.4.16.4 serine-type D-Ala-D-Ala carboxypeptidase
EC 3.4.16.5 carboxypeptidase C
EC 3.4.16.6 carboxypeptidase D
[EC 3.4.16.1 Transferred entry: now EC 3.4.16.5 - carboxypeptidase C, and EC 3.4.16.6 - carboxypeptidase D (EC 3.4.16.1 created 1972 as EC 3.4.12.1 and EC 3.4.21.13, both transferred 1978 to EC 3.4.16.1, deleted 1993)]
Accepted name: lysosomal Pro-Xaa carboxypeptidase
Reaction: Cleavage of a -ProXaa bond to release a C-terminal amino acid
Other names: angiotensinase C; lysosomal carboxypeptidase C; peptidylprolylamino acid carboxypeptidase; aminoacylproline carboxypeptidase; prolyl carboxypeptidase; carboxypeptidase P; proline-specific carboxypeptidase P; PCP; lysosomal Pro-Xaa carboxypeptidase
Comments: A lysosomal peptidase active at acidic pH that inactivates angiotensin II. Inhibited by diisopropyl fluorophosphate. In peptidase family S28 (Pro-X carboxypeptidase family). Formerly EC 3.4.12.4
Links to other databases: BRENDA, EXPASY, KEGG, MEROPS, Metacyc, PDB, CAS registry number: 9075-64-3
References
1. Walter, R., Simmons, W.H. and Yoshimoto, T. Proline specific endo- and exopeptidases. Mol. Cell. Biochem. 30 (1980) 111-127. [=: 6991912]
2. Odya, C.E. and Erdös, E.G. Human prolylcarboxypeptidase. Methods Enzymol. 80 (1981) 460-466. [PMID: 7341916]
[EC 3.4.16.3 Transferred entry: now included with EC 3.4.16.5 - carboxypeptidase C [EC 3.4.16.3 created 1972 as EC 3.4.12.12, transferred 1978 to EC 3.4.16.3, deleted 1992]]
Accepted name: serine-type D-Ala-D-Ala carboxypeptidase
Reaction: Preferential cleavage: (Ac)2-L-Lys-D-AlaD-Ala. Also transpeptidation of peptidyl-alanyl moieties that are N-acyl substituents of D-alanine
Other names: DD-peptidase; D-alanyl-D-alanine-carboxypeptidase; D-alanyl-D-alanine-cleaving-peptidase; D-alanyl-D-alanine-cleaving peptidase; DD-transpeptidase; D-alanine carboxypeptidase; DD-carboxypeptidase; D-alanyl carboxypeptidase
Comments: A membrane-bound, bacterial enzyme inhibited by penicillin and other β-lactam antibiotics, which acylate the active site serine. Examples are known from peptidase families S11, S12 and S13. Distinct from EC 3.4.17.14, zinc D-Ala-D-Ala carboxypeptidase
Links to other databases: BRENDA, EXPASY, KEGG, MEROPS, Metacyc, PDB, CAS registry number: 9077-67-2
References
1. Ghuysen, J.-M., Frère, J.-M., Leyh-Bouille, M., Nguyen-Distèche, M., Coyette, J., Dusart, J., Joris, B., Duez, C., Dideberg, O., Charlier, P., Dive, G., and Lamotte-Brasseur, J. Bacterial wall peptidoglycan, DD-peptidases and beta-lactam antibiotics. Scand. J. Infect. Dis. Suppl. 42 (1984) 17-37. [PMID: 6597561]
2. Frère, J.M. and Joris, B. Penicillin-sensitive enzymes in peptidoglycan biosynthesis. CRC Crit. Rev. Microbiol. 11 (1985) 306-331. [PMID: 3888533]
Accepted name: carboxypeptidase C
Reaction: Release of a C-terminal amino acid with broad specificity
Other names: carboxypeptidase Y; serine carboxypeptidase I; cathepsin A; lysosomal protective protein; deamidase; lysosomal carboxypeptidase A; phaseolin
Comments: A carboxypeptidase with optimum pH 4.5-6.0, inhibited by diisopropyl fluorophosphate, and sensitive to thiol-blocking reagents (reviewed in [1]). Widely distributed in eukaryotes. Type example of peptidase family S10. Formerly EC 3.4.12.1 and EC 3.4.21.13, and included in EC 3.4.16.1.
Links to other databases: BRENDA, EXPASY, KEGG, MEROPS, Metacyc, PDB, CAS registry number: 9046-67-7
References
1. Breddam, K. Serine carboxypeptidases. A review. Carlsberg Res. Commun. 51 (1986) 83-128
2. Valls, L.A., Hunter, C.P., Rothman, J.H. and Stevens, T.H. Protein sorting in yeast: the localization determinant of yeast vacuolar carboxypeptidase Y resides in the propeptide. Cell 48 (1987) 887-897. [PMID: 3028649]
3. Jackman, H.L., Morris, P.W., Deddish, P.A., Skidgel, R.A. and Erdös, E.G. Inactivation of endothelin I by deamidase (lysosomal protective protein). J. Biol. Chem. 267 (1992) 2872-2875. [PMID: 1737744]
4. Miller, J.J., Changaris, D.G. and Levy, R.S. Purification, subunit structure and inhibitor profile of cathepsin-A. J. Chromatogr. 627 (1992) 153-162. [PMID: 1487525]
Accepted name: carboxypeptidase D
Reaction: Preferential release of a C-terminal arginine or lysine residue
Other name(s): cereal serine carboxypeptidase II; Saccharomyces cerevisiae KEX1 gene product; carboxypeptidase Kex1; gene KEX1 serine carboxypeptidase; KEX1 carboxypeptidase; KEX1 proteinase; KEX1DELTAp; CPDW-II; serine carboxypeptidase (misleading); Phaseolus proteinase
Comments: A carboxypeptidase with optimum pH 4.5-6.0, inhibited by diisopropyl fluorophosphate, and sensitive to thiol-blocking reagents (reviewed in [1]). In peptidase family S10 (carboxypeptidase C family).
Links to other databases: BRENDA, EXPASY, KEGG, MEROPS, Metacyc, PDB, CAS registry number: 153967-26-1
References:
1. Breddam, K. Serine carboxypeptidases. A review. Carlsberg Res. Commun. 51 (1986) 83-128.
2. Breddam, K., Sørensen, S.B. and Svendsen, I. Primary structure and enzymatic properties of carboxypeptidase II from wheat bran. Carlsberg Res. Commun. 52 (1987) 297-311.
3. Dmochowska, A., Dignard, D., Henning, D., Thomas, D.Y. and Bussey, H. Yeast KEX1 gene encodes a putative protease with a carboxypeptidase B-like function involved in killer toxin and α-factor precursor processing. Cell 50 (1987) 573-584. [PMID: 3301004]
4. Liao, D.-I., Breddam, K., Sweet, R.M., Bullock, T. and Remington, S.J. Refined atomic model of wheat serine carboxypeptidase II at 2.2-Å resolution. Biochemistry 31 (1992) 9796-9812. [PMID: 1390755]
Contents
EC 3.4.17.1 carboxypeptidase A
EC 3.4.17.2 carboxypeptidase B
EC 3.4.17.3 lysine carboxypeptidase
EC 3.4.17.4 Gly-Xaa carboxypeptidase
EC 3.4.17.5 deleted
EC 3.4.17.6 alanine carboxypeptidase
EC 3.4.17.7 now EC 3.4.19.10
EC 3.4.17.8 muramoylpentapeptide carboxypeptidase
EC 3.4.17.9 deleted, included in EC 3.4.17.4
EC 3.4.17.10 carboxypeptidase E
EC 3.4.17.11 glutamate carboxypeptidase
EC 3.4.17.12 carboxypeptidase M
EC 3.4.17.13 muramoyltetrapeptide carboxypeptidase
EC 3.4.17.14 zinc D-Ala-D-Ala carboxypeptidase
EC 3.4.17.15 carboxypeptidase A2
EC 3.4.17.16 membrane Pro-Xaa carboxypeptidase
EC 3.4.17.17 tubulinyl-Tyr carboxypeptidase
EC 3.4.17.18 carboxypeptidase T
EC 3.4.17.19 carboxypeptidase Taq
EC 3.4.17.20 carboxypeptidase U
EC 3.4.17.21 glutamate carboxypeptidase II
EC 3.4.17.22 metallocarboxypeptidase D
EC 3.4.17.23 angiotensin-converting enzyme 2
EC 3.4.17.24 tubulin-glutamate carboxypeptidase
EC 3.4.17.25 glutathione-S-conjugate glycine hydrolase
Accepted name: carboxypeptidase A
Reaction: Release of a C-terminal amino acid, but little or no action with -Asp, -Glu, -Arg, -Lys or -Pro
Other names: carboxypolypeptidase; pancreatic carboxypeptidase A; tissue carboxypeptidase A
Comments: A zinc enzyme formed from procarboxypeptidase A. Isolated from cattle, pig and dogfish pancreas, and other sources including mast cells [3] and skeletal muscle [4]. Type example of peptidase family M14. Formerly EC 3.4.2.1 and EC 3.4.12.2
Links to other databases: BRENDA, EXPASY, GTD, KEGG, MEROPS, Metacyc, PDB, CAS registry number: 11075-17-5
References
1. Petra, P.H. Bovine procarboxypeptidase and carboxypeptidase A. Methods Enzymol. 19 (1970) 460-503
2. Reeck, G.R., Walsh, K.A. and Neurath, H. Isolation and characterization of carboxypeptidases A and B from activated pancreatic juice. Biochemistry 10 (1971) 4690-4698. [PMID: 5140186]
3. Everitt, M.T. and Neurath, H. Rat peritoneal mast cell carboxypeptidase: localization, purification and enzymatic properties. FEBS Lett. 110 (1980) 292-296. [PMID: 7371832]
4. Bodwell, J.E. and Meyer, W.L. Purification and characterization of carboxypeptidase A from rat skeletal muscle. Biochemistry 20 (1981) 2767-2777. [PMID: 7018567]
Accepted name: carboxypeptidase B
Reaction: Preferential release of a C-terminal lysine or arginine amino acid
Other names: protaminase; pancreatic carboxypeptidase B; tissue carboxypeptidase B; peptidyl-L-lysine [L-arginine]hydrolase
Comments: A zinc enzyme formed from procarboxypeptidase B. Isolated from cattle, pig and dogfish pancreas and other sources, including skin fibroblasts [3] and adrenal medulla [4]. In peptidase family M14 (carboxypeptidase A family). Formerly EC 3.4.2.2 and EC 3.4.12.3
Links to other databases: BRENDA, EXPASY, KEGG, MEROPS, Metacyc, PDB, CAS registry number: 9025-24-5
References
1. Folk, J.E. Carboxypeptidase B (porcine pancreas). Methods Enzymol. 19 (1970) 504-508
2. Brodrick, J.W., Geokas, M.C. and Largman, C. Human carboxypeptidase B. II. Purification of the enzyme from pancreatic tissue and comparison with the enzymes present in pancreatic secretion. Biochim. Biophys. Acta 452 (1976) 468-481. [PMID: 1009123]
3. Butterworth, J. and Duncan, J.J. Carboxypeptidase B activity of cultured skin fibroblasts and relationship to cystic fibrosis. Clin. Chim. Acta 97 (1979) 39-43. [PMID: 40714]
4. Wallace, E.F., Evans, C.J., Jurik, S.M., Mefford, I.N. and Barchas, J.D. Carboxypeptidase B activity from adrenal medulla. Is it involved in the processing of proenkephalin? Life Sci. 31 (1982) 1793-1796. [PMID: 6130442]
Accepted name: lysine carboxypeptidase
Reaction: Release of a C-terminal basic amino acid, preferentially lysine
Other names: carboxypeptidase N; arginine carboxypeptidase; kininase I; anaphylatoxin inactivator; plasma carboxypeptidase B; creatine kinase conversion factor; bradykinase; kininase Ia; hippuryllysine hydrolase; bradykinin-decomposing enzyme; protaminase; CPase N; creatinine kinase convertase; peptidyl-L-lysine(-L-arginine) hydrolase; CPN
Comments: A zinc enzyme found in plasma. Inactivates bradykinin and anaphylatoxins in blood plasma. In peptidase family M14 (carboxypeptidase A family). Formerly EC 3.4.12.7
Links to other databases: BRENDA, EXPASY, KEGG, MEROPS, Metacyc, PDB, CAS registry number: 9013-89-2
References
1. Plummer, T.H., Jr and Erdös, E.G. Human plasma carboxypeptidase N. Methods Enzymol. 80 (1981) 442-449. [PMID: 7341915]
2. Levin, Y., Skidgel, R.A. and Erdös, E.G. Isolation and characterization of the subunits of human plasma carboxypeptidase N (kininase I). Proc. Natl. Acad. Sci. USA 79 (1982) 4618-4622. [PMID: 6750606]
3. Skidgel, R.A. Basic carboxypeptidases: regulators of peptide hormone activity. Trends Pharmacol. Sci. 9 (1988) 301-303. [PMID: 3074547]
Accepted name: Gly-Xaa carboxypeptidase
Reaction: Release of a C-terminal amino acid from a peptide in which glycine is the penultimate amino acid, e.g. Z-GlyLeu
Other names: glycine carboxypeptidase; carboxypeptidase a; carboxypeptidase S; peptidase α; yeast carboxypeptidase; Gly-X carboxypeptidase
Comments: From yeast. In peptidase family M20 (glutamate carboxypeptidase family). Formerly EC 3.4.2.3, EC 3.4.12.8 and EC 3.4.17.9
Links to other databases: BRENDA, EXPASY, KEGG, GTD, MEROPS, Metacyc, CAS registry number: 9025-25-6
References
1. Félix, F. and Brouillet, N. Purification et proprietes de deux peptidases de levure de brasserie. Biochim. Biophys. Acta 122 (1966) 127-144. [PMID: 4961236]
2. Wolf, D.H. and Ehmann, C. Carboxypeptidase S from yeast: regulation of its activity during vegetative growth and differentiation. FEBS Lett. 91 (1978) 59-62. [PMID: 352726]
[EC 3.4.17.5 Deleted entry: aspartate carboxypeptidase [EC 3.4.17.5 created 1972 as EC 3.4.12.9, transferred 1978 to EC 3.4.17.5, deleted 1992]]
Accepted name: alanine carboxypeptidase
Reaction: Release of a C-terminal alanine from a peptide or a variety of pteroyl or acyl groups
Other names: N-benzoyl-L-alanine-amidohydrolase
Comments: From soil bacteria. The enzyme from Corynebacterium equi also hydrolyses N-benzoylglycine and N-benzoyl-L-aminobutyric acid. Formerly EC 3.4.12.11
Links to other databases: BRENDA, EXPASY, KEGG, MEROPS, Metacyc, CAS registry number: 37288-70-3
References
1. Levy, C.C. and Goldman, P. Bacterial peptidases. J. Biol. Chem. 244 (1969) 4467-4472. [PMID: 5806587]
2. Miyagawa, E., Takahiro, H. and Yoshinobu, M. Purification and properties of N-benzoyl-L-alanine amidohydrolase from Corynebacterium equii. Agric. Biol. Chem. 50 (1986) 1527-1531
[EC 3.4.17.7 Transferred entry: now EC 3.5.1.28 - N-acetylmuramoyl-L-alanine amidase [EC 3.4.17.7 created 1978, deleted 1992]]
Accepted name: muramoylpentapeptide carboxypeptidase
Reaction: Cleavage of the bond UDP-N-acetylmuramoyl-L-alanyl-γ-D-glutamyl-6-carboxy-L-lysyl-D-alanylD-alanine
Other name(s): D-alanine carboxypeptidase I; DD-carboxypeptidase; D-alanine carboxypeptidase; D-alanyl-D-alanine carboxypeptidase; D-alanine-D-alanine-carboxypeptidase; carboxypeptidase D-alanyl-D-alanine; carboxypeptidase I; UDP-N-acetylmuramoyl-tetrapeptidyl-D-alanine alanine-hydrolase; D-alanyl-D-alanine peptidase; DD-peptidase; penicillin binding protein 5; PBP5; PdcA; VanY; VanX (ambiguous)
Comments: A bacterial enzyme that requires a divalent cation for activity. Does not cleave the C-terminal D-alanine from the product of the above reaction, UDP-N-acetyl-muramoyl-L-alanyl-D-γ-glutamyl-6-carboxy-L-lysyl-D-alanine. Competitively inhibited by penicillins and cephalosporins.
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, PDB, CAS registry number: 9077-67-2
References:
1. Izaki, K. and Strominger, J.L. Biosynthesis of the peptidoglycan of bacterial cell walls. XIV. Purification and properties of two D-alanine carboxypeptidases from Escherichia coli. J. Biol. Chem. 243 (1968) 3193-3201. [PMID: 4871206]
[EC 3.4.17.9 Transferred entry: now included with EC 3.4.17.4 - Gly-Xaa carboxypeptidase [EC 3.4.17.9 created 1981, deleted 1992]]
Accepted name: carboxypeptidase E
Reaction: Release of C-terminal arginine or lysine residues from polypeptides
Other names: carboxypeptidase H; enkephalin convertase; cobalt-stimulated chromaffin granule carboxypeptidase; insulin granule-associated carboxypeptidase; enkephalin convertase; membrane-bound carboxypeptidase; carboxypeptidase E; enkephalin-precursor endopeptidase; enkephalin precursor carboxypeptidase; peptidyl-L-lysine(-L-arginine) hydrolase
Comments: A zinc enzyme, activated by Co2+. Inhibited by 1,10-phenanthroline and other chelating agents. pH optimum 5.6. Located in storage granules of secretory cells, and active in processing of protein hormones and bioactive peptides. In peptidase family M14 (carboxypeptidase A family). Formerly EC 3.4.17.10, carboxypeptidase H
Links to other databases: BRENDA, EXPASY, KEGG, MEROPS, Metacyc, CAS registry number: 81876-95-1
References
1. Qian, Y.M., Varlamov, O. and Fricker, L.D. Glu300 of rat carboxypeptidase E is essential for enzymatic activity but not substrate binding or routing to the regulated secretory pathway. J. Biol. Chem. 274 (1999) 11582-11586. [PMID: 10206965]
2. Fricker, L.D. Carboxypeptidase E/H. In Handbook of Proteolytic Enzymes (Barrett, A.J., Rawlings, N.D. and Woessner, J.F. eds), p.1341-1344 (1998) Academic Press, London.
3. Fricker, L.D. Methods for studying carboxypeptidase E. Methods Neurosci. 23 (1995) 237-250.
4. Manser, E., Fernandez, D., Loo,L., Goh, P.Y., Monfries, C., Hall, C. and Lim,L. Human carboxypeptidase E: isolation and characterisaton of the cDNA, sequence conservation, expression and processing in vitro. Biochem. J. 267 (1990) 517-525. [PMID: 2334405]
5. Fricker, L.D. Carboxypeptidase E. Annu. Rev. Physiol. 50 (1988) 309-321. [PMID: 2897826]
Accepted name: glutamate carboxypeptidase
Reaction: Release of C-terminal glutamate residues from a wide range of N-acylating moieties, including peptidyl, aminoacyl, benzoyl, benzyloxycarbonyl, folyl and pteroyl groups
Other names: carboxypeptidase G; carboxypeptidase G1; carboxypeptidase G2; glutamyl carboxypeptidase; N-pteroyl-L-glutamate hydrolase
Comments: A zinc enzyme produced by pseudomonads, Flavobacterium sp. and Acinetobacter sp. Its ability to hydrolyse pteroyl-L-glutamate (folic acid) has led to its use as a folate-depleting, antitumour agent. Type example of peptidase family M20
Links to other databases: BRENDA, EXPASY, KEGG, MEROPS, Metacyc, PDB, CAS registry number: 9074-87-7
References
1. Goldman, P. and Levy, C.C. Carboxypeptidase G: purification and properties. Proc. Natl. Acad. Sci. USA 58 (1967) 1299-1306 [PMID: 5237864]
2. McCullogh, J.L., Chabner, B.A. and Bertino, J.R. Purification and properties of carboxypeptidase G1. J. Biol. Chem. 246 (1971) 7207-7213. [PMID: 5129727]
3. Albrecht, A.M., Boldizar, E. and Hutchinson, D.J. Carboxypeptidase displaying differential velocity in hydrolysis of methotrexate, 5-methyltetrahydrofolic acid, and leucovorin. J. Bacteriol. 134 (1978) 506-513. [PMID: 26657]
4. Sherwood, R.F., Melton, R.G. and Alwan, S.A. Purification and properties of carboxypeptidase G2 from Pseudomonas sp. strain RS-16. Eur. J. Biochem. 148 (1985) 447-453. [PMID: 3838935]
Accepted name: carboxypeptidase M
Reaction: Cleavage of C-terminal arginine or lysine residues from polypeptides
Other name(s): CPM
Comments: A membrane-bound enzyme optimally active at neutral pH. In peptidase family M14 (carboxypeptidase A family)
Links to other databases: BRENDA, EXPASY, KEGG, MEROPS, Metacyc, PDB, CAS registry number: 120038-28-0
References
1. Skidgel, R.A. Basic carboxypeptidases: Regulators of peptide hormone activity. Trends Pharmacol. Sci. 9 (1988) 303-304. [PMID: 3074547]
2. Deddish, P.A., Skidgel, R.A. and Erdös, E.G. Enhanced Co2+ activation and inhibitor binding of carboxypeptidase M at low pH. Biochem. J. 261 (1989) 289-291. [PMID: 2775217]
3. Skidgel, R.A., Davis, R.M. and Tan, F. Human carboxypeptidase M. Purification and characterization of membrane-bound carboxypeptidase that cleaves peptide hormones. J. Biol. Chem. 264 (1989) 2236-2241. [PMID: 2914904]
Accepted name: muramoyltetrapeptide carboxypeptidase
Reaction: Hydrolysis of the bond: N-acetyl-D-glucosaminyl-N-acetylmuramoyl-L-Ala-D-glutamyl-6-carboxy-L-lysylD-alanine
Other names: carboxypeptidase IIW; carboxypeptidase II; lysyl-D-alanine carboxypeptidase; L-lysyl-D-alanine carboxypeptidase; LD-carboxypeptidase
Comments: Variants are known from various microorganisms. Involved in peptidoglycan synthesis, catalysing both decarboxylation and transpeptidation. Stimulated by divalent cations such as Mg2+ and Ca2+, but not by Zn2+. Inhibited by thiol-blocking reagents, but unaffected by penicillin
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, PDB, CAS registry number: 60063-80-1
References
1. DasGupta, H. and Fan, D.P. Purification and characterization of a carboxypeptidase-transpeptidase of Bacillus megaterium acting on the tetrapeptide moiety of the peptidoglycan. J. Biol. Chem. 254 (1979) 5672-5683. [PMID: 109439]
2. Rousset, A., Nguyen-Disteche, M., Minck, R. and Ghuysen, J.-M. Penicillin-binding proteins and carboxypeptidase/transpeptidase activities in Proteus vulgaris P18 and its penicillin-induced stable L-forms. J. Bacteriol. 152 (1982) 1042-1048. [PMID: 6754695]
3. Metz, R., Henning, S. and Hammes, W.P. LD-Carboxypeptidase activity in Escherichia coli. II. Isolation, purification and characterization of the enzyme from E. coli K 12. Arch. Microbiol. 144 (1986) 181-186
Accepted name: zinc D-Ala-D-Ala carboxypeptidase
Reaction: Cleavage of the bond: (Ac)2-L-lysyl-D-alanylD-alanine
Other names: Zn2+ G peptidase; D-alanyl-D-alanine hydrolase; D-alanyl-D-alanine-cleaving carboxypeptidase; DD-carboxypeptidase; G enzyme; DD-carboxypeptidase-transpeptidase
Comments: A zinc enzyme. Catalyzes carboxypeptidation but not transpeptidation reactions involved in bacterial cell wall metabolism. Weakly inhibited by β-lactams. In peptidase family M15. Distinct from EC 3.4.16.4, serine-type D-Ala-D-Ala carboxypeptidase.
Links to other databases: BRENDA, EXPASY, KEGG, MEROPS, Metacyc, PDB, CAS registry number: 213189-85-6
References
1. Dideberg, O., Charlier, P., Dive, G., Joris, B., Frère, J.M. and Ghuysen, J.M. Structure of a Zn2+-containing D-alanyl-D-alanine-cleaving carboxypeptidase at 2.5 Å resolution. Nature 299 (1982) 469-470. [PMID: 7121588]
2. Joris, B., Van Beeumen, J., Casagrande, F., Gerday, C., Frère, J.-M. and Ghuysen, J.-M. The complete amino acid sequence of the Zn2+-containing D-alanyl-D-alanine-cleaving carboxypeptidase of Streptomyces albus G. Eur. J. Biochem. 130 (1983) 53-69[PMID: 6825689]
3. Ghuysen, J.-M., Frère, J.-M., Leyh-Bouille, M., Nguyen-Disteche, M., Coyette, J., Dusart, J., Joris, B., Duez, C., Dideberg, O., Charlier, P., Dive, G. and Lamotte-Brasseur, J. Bacterial wall peptidoglycan, DD-peptidases and beta-lactam antibiotics. Scand. J. Infect. Dis. Suppl. 42 (1984) 17-37. [PMID: 6597561]
Accepted name: carboxypeptidase A2
Reaction: Similar to that of carboxypeptidase A (EC 3.4.17.1), but with a preference for bulkier C-terminal residues
Other name(s): CPA2
Comments: Isolated from rat pancreas but not present in cattle pancreas. In peptidase family M14 (carboxypeptidase A family)
Links to other databases: BRENDA, EXPASY, KEGG, MEROPS, Metacyc, PDB, CAS registry number: 181186-98-1
References
1. Gardell, S.J., Craik, C.S., Clauser, E., Goldsmith, E.J., Stewart, C.-B., Graf, M. and Rutter, W.J. A novel rat carboxypeptidase, CPA2: characterization, molecular cloning, and evolutionary implications on substrate specificity in the carboxypeptidase gene family. J. Biol. Chem. 263 (1988) 17828-17836. [PMID: 5500406]
Accepted name: membrane Pro-Xaa carboxypeptidase
Reaction: Release of a C-terminal residue other than proline, by preferential cleavage of a prolyl bond
Other names: carboxypeptidase P; microsomal carboxypeptidase; membrane Pro-X carboxypeptidase
Comments: One of the renal brush border exopeptidases
Links to other databases: BRENDA, EXPASY, KEGG, MEROPS, Metacyc, CAS registry number: 9075-64-3
References
1. Dehm, P. and Nordwig, A. The cleavage of prolyl peptides by kidney peptidases. Isolation of a microsomal carboxypeptidase from swine kidney. Eur. J. Biochem. 17 (1970) 372-377. [PMID: 5500406]
2. Booth, A.G., Hubbard, L.M.L. and Kenny, A.J. Proteins of the kidney microvillar membrane. Immunoelectrophoretic analysis of the membrane hydrolase: identification and resolution of the detergent- and proteinase-solubilized forms. Biochem. J. 179 (1979) 397-405. [PMID: 486090]
3. Hedeager-Sorensen, S. and Kenny, A.J. Proteins of the kidney microvillar membrane. Purification and properties of carboxypeptidase P from pig kidneys. Biochem. J. 229 (1985) 251-257. [PMID: 4038259]
Accepted name: tubulinyl-Tyr carboxypeptidase
Reaction: Cleavage of the -GluTyr bond to release the C-terminal tyrosine residue from the native tyrosinated tubulin. Inactive on Z-Glu-Tyr
Other name(s): carboxypeptidase-tubulin; soluble carboxypeptidase; tubulin-tyrosine carboxypeptidase; tubulin carboxypeptidase; tubulinyltyrosine carboxypeptidase; tyrosinotubulin carboxypeptidase; tyrosyltubulin carboxypeptidase; TTCPase; brain I carboxypeptidase; carboxypeptidase 1; CCP1
Comments: Active at neutral pH, from brain
Links to other databases: BRENDA, EXPASY, KEGG, MEROPS, Metacyc, PDB, CAS registry number: 73050-23-4
References
1. Argaraña, C.E., Barra, H.S. and Caputto, R. Tubulinyl-tyrosine carboxypeptidase J. Neurochem. 34 (1980) 114-118. [PMID: 7452228]
2. Kumar, N. and Flavin, M. Preferential action of a brain detyrosinolating carboxypeptidase on polymerized tubulin. J. Biol. Chem. 256 (1981) 7678-7686. [PMID: 6114100]
3. Arce, C.A. and Barra, H.S. Association of tubulinyl-tyrosine carboxypeptidase with microtubules. FEBS Lett. 157 (1983) 75-78. [PMID: 6862022]
4. Berezniuk, I., Lyons, P.J., Sironi, J.J., Xiao, H., Setou, M., Angeletti, R.H., Ikegami, K. and Fricker, L.D. Cytosolic carboxypeptidase 5 removes α- and γ-linked glutamates from tubulin. J. Biol. Chem. 288 (2013) 30445–30453. [PMID: 24022482]
Accepted name: carboxypeptidase T
Reaction: Releases a C-terminal residue, which may be hydrophobic or positively charged
Other name(s): CPT (ambiguous)
Comments: Known from Thermoactinomyces vulgaris. In peptidase family M14 (carboxypeptidase A family)
Links to other databases: BRENDA, EXPASY, KEGG, MEROPS, Metacyc, PDB, CAS registry number: 89623-65-4
References
1. Osterman, A.L., Stepanov, V.M., Rudenskaya, G.N., Khodova, O.M., Tsaplina, I.A., Yakovleva, M.B. and Loginova, L.G. Carboxypeptidase T - an extracellular carboxypeptidase of thermophilic actinomycetes - a remote analog of animal carboxypeptidases. Biochemistry (USSR) 49 (1984) 292-301. [PMID: 6424730]
2. Smulevitch, S.V., Osterman, A.L., Galperina, O.V., Matz, M.V., Zagnitko, O.P., Kadyrov, R.M., Tsaplina, I.A., Grishin, N.V., Chestukhina, G.G. and Stepanov, V.M. Molecular cloning and primary structure of Thermoactinomyces vulgaris carboxypeptidase T: a metalloenzyme endowed with dual substrate specificity. FEBS Lett. 291 (1991) 75-78. [PMID: 1936254]
3. Teplyakov, A., Polyakov, K., Obmolova, G., Strokopytov, B., Kuranova, I., Osterman, A., Grishin, N., Smulevitch, S., Zagnitko, O., Galperina, O., Matz, M. and Stepanov, V. Crystal structure of carboxypeptidase T from Thermoactinomyces vulgaris. Eur. J. Biochem. 208 (1992) 281-288. [PMID: 1521526]
Accepted name: carboxypeptidase Taq
Reaction: Release of a C-terminal amino acid with broad specificity, except for -Pro
Comments: A 56-kDa enzyme from Thermus aquaticus. Most active at 80° C. Type example of peptidase family M32
Links to other databases: BRENDA, EXPASY, KEGG, MEROPS, Metacyc, CAS registry number: 9031-98-5
References
1. Lee, S.-H., Minagawa, E., Taguchi, H., Matsuzawa, H., Ohta, T., Kaminogawa, S. and Yamauchi, K. Purification and characterization of a thermostable carboxypeptidase (carboxypeptidase Taq) from Thermus aquaticus YT-1. Biosci. Biotechnol. Biochem. 56 (1992) 1839-1844 [PMID: 1369078]
2. Lee, S.-H., Taguchi, H., Yoshimura, E., Minagawa, E., Kaminogawa, S., Ohta, T. and Matsuzawa, H. Carboxypeptidase Taq, a thermostable zinc enzyme, from Thermus aquaticus YT-1: molecular cloning, sequencing, and expression of the encoding gene in Escherichia coli. Biosci. Biotechnol. Biochem. 58 (1994) 1490-1495 [PMID: 7765282]
Accepted name: carboxypeptidase U
Reaction: Release of C-terminal Arg and Lys from a polypeptide
Other names: arginine carboxypeptidase; carboxypeptidase R; plasma carboxypeptidase B (misleading, since the term carboxypeptidase B is used for other enzymes); thrombin-activatable fibrinolysis inhibitor
Comments: Pro-carboxypeptidase U in (human) plasma is activated by thrombin or plasmin during clotting to form the unstable carboxypeptidase U, with activity similar to that of the more stable lysine carboxypeptidase, except that no preference is shown for Lys over Arg. A zinc enzyme, In peptidase family M14 (carboxypeptidase A family)
Links to other databases: BRENDA, EXPASY, KEGG, MEROPS, Metacyc, CAS registry number: 156621-18-0
References
1. Eaton, D.L., Malloy, B.E., Tsai, S.P., Henzel, W. and Drayna, D. Isolation, molecular cloning, and partial characterization of a novel carboxypeptidase B from human plasma. J. Biol. Chem. 266 (1991) 21833-21838. [PMID: 1939207]
2. Shinohara, T., Sakurada, C., Suzuki, T., Takeuchi, O., Campbell, W., Ikeda, S., Okada, N. and Okada, H. Pro-carboxypeptidase R cleaves bradykinin following activation. Int. Arch. Allergy Immunol. 103 (1994) 400-404. [PMID: 8130654]
3. Wang, W., Hendriks, D.F. and Scharpé, S. Carboxypeptidase U, a plasma carboxypeptidase with high affinity for plasminogen. J. Biol. Chem. 269 (1994) 15937-15944. [PMID: 8195249]
4. Tan, A.K. and Eaton, D.L. Activation and characterization of procarboxypeptidase B from human plasma. Biochemistry 34 (1995) 5811-5816. [PMID: 7727441]
5. Broze, G.J., Jr. and Higuchi, D.A. Coagulation-dependent inhibition of fibrinolysis: Role of carboxypeptidase U and the premature lysis of clots from hemophilic plasma. Blood 88 (1996) 3815-3823. [PMID: 8916945]
Accepted name: glutamate carboxypeptidase II
Reaction: Release of an unsubstituted, C-terminal glutamyl residue, typically from Ac-Asp-Glu or folylpoly-γ-glutamates
Glossary entries:
quisqualic acid = 3-(3,5-dioxo-1,2,4-oxazadiazolidin-2-yl)Ala
Other names: N-acetylated-γ-linked-acidic dipeptidase (NAALADase); folate hydrolase; prostate-specific membrane antigen; pteroylpoly-γ-glutamate carboxypeptidase; microsomal γ-glutamyl carboxypeptidase; pteroylpolyglutamate hydrolase; folylpolyglutamate hydrolase; pteroylpoly-γ-glutamate hydrolase; pteroylpolygammaglutamyl hydrolase; pteroylpolyglutamate hydrolase; pteroylpolyglutamic acid hydrolase; PSM antigen; acetylaspartylglutamate dipeptidase; NAALA dipeptidase; rat NAAG peptidase; mGCP; membrane glutamate carboxypeptidase; N-acetylated-α-linked-amino dipeptidase; prostrate-specific membrane antigen; N-Acetylated α-linked acidic dipeptidase; PSMA
Comments: A metallo-carboxypeptidase that is predominantly expressed as a membrane-bound enzyme of 94-100 kDa , but also exists in a soluble form. Hydrolyses α-peptide bonds in Ac-Asp-Glu, Asp-Glu, and Glu-Glu, but also γ-glutamyl bonds in γ-Glu-Glu, and folylpoly-γ-glutamates. With folylpoly-γ-glutamates, shows processive carboxypeptidase activity to produce pteroylmonoglutamate [4]. Does not hydrolyse Ac-β-Asp-Glu. Known inhibitors: quisqualic acid, Ac-β-Asp-Glu, and 2-phosphonomethyl-pentanedioate. In peptidase family M28 of Vibrio leucyl aminopeptidase. Formerly EC 3.4.19.8. The release of C-terminal glutamate from folylpoly-γ-glutamates is also catalysed by EC 3.4.17.11 (glutamate carboxypeptidase) and EC 3.4.19.9 (γ-Glu-X carboxypeptidase).
Links to other databases: BRENDA, EXPASY, KEGG, MEROPS, Metacyc, CAS registry number: 9074-87-7
References
1. Heston, W.D.W. Characterization and glutamyl preferring carboxypeptidase function of prostate specific membrane antigen: a novel folate hydrolase. Urology 49 (1997) 104-112. [PMID: 9123729]
2. Rawlings, N.D. and Barrett, A.J. Structure of membrane glutamate carboxypeptidase. Biochim. Biophys. Acta 1339 (1997) 247-252. [PMID: 9187245]
3. Halsted, C.H., Ling, E.-H., Luthi-Carter, R., Villanueva, J.A., Gardner, J.M., Coyle, J.T. Folylpoly-γ-glutamate carboxypeptidase from pig jejunum: molecular characterization and relation to glutamate carboxypeptidase II. J. Biol. Chem. 273 (1998) 20417-20424. [PMID: 9685395]
4. Luthi-Carter, R., Berger, U.V., Barczak, A.K., Enna, M. and Coyle, J.T. Isolation and expression of a rat brain cDNA encoding glutamate carboxypeptidase II. Proc. Natl. Acad. Sci. USA 95 (1998) 3215-3220.. [PMID: 9501243]
Accepted name: metallocarboxypeptidase D
Reaction: Releases C-terminal Arg and Lys from polypeptides
Other names: carboxypeptidase D (cattle, human, mouse, rat); gp180 (duck)
Comments: Activated by Co2+; inhibited by guanidinoethylmercaptosuccinic acid. Large molecule (180 kDa) because of presence of three copies of metallopeptidase domain. The product of the silver gene (Drosophila) is similar. A zinc metallopeptidase In peptidase family M14 (carboxypeptidase A family)
Links to other databases: BRENDA, EXPASY, KEGG, MEROPS, Metacyc, CAS registry number: 153967-26-1
References
1. Kuroki, K., Eng, F., Ishikawa, T., Turck, C., Harada, F. and Ganem, D. gp180, a host cell glycoprotein that binds duck hepatitis B virus particles, is encoded by a member of the carboxypeptidase gene family. J. Biol. Chem. 270 (1995) 15022-15028.[PMID: 9525948]
2. Song, L.X. and Fricker, L.D. Purification and characterization of carboxypeptidase D, a novel carboxypeptidase E-like enzyme, from bovine pituitary. J. Biol. Chem. 270 (1995) 25007-25013[PMID: 7559630]
3. Song, L.X. and Fricker, L.D. Tissue distribution and characterization of soluble and membrane-bound forms of metallocarboxypeptidase D. J. Biol. Chem. 271 (1996) 28884-28889[PMID: 8910535]
Accepted name: angiotensin-converting enzyme 2
Reaction: angiotensin II + H2O = angiotensin-(1-7) + L-phenylalanine
Other name(s): ACE-2; ACE2; hACE2; angiotensin converting enzyme 2; angiotensin converting enzyme-2; Tmem27
Comments: A transmembrane glycoprotein with an extracellular catalytic domain. Angiotensin-converting enzyme 2 functions as a carboxypeptidase, cleaving a single C-terminal residue from a distinct range of substrates [2]. Catalytic efficiency is 400-fold higher with angiotensin II (1-8) as a substrate than with angiotensin I (1-10). Angiotensin-converting enzyme 2 also efficiently hydrolyzes des-Arg9-bradykinin, but it does not hydrolyze bradykinin [1]. In peptidase family M2.
Links to other databases: BRENDA, EXPASY, KEGG, MEROPS, Metacyc, PDB, CAS registry number:
References:
1. Vickers, C., Hales, P., Kaushik, V., Dick, L., Gavin, J., Tang, J., Godbout, K., Parsons, T., Baronas, E., Hsieh, F., Acton, S., Patane, M., Nichols, A. and Tummino, P. Hydrolysis of biological peptides by human angiotensin-converting enzyme-related carboxypeptidase. J. Biol. Chem. 277 (2002) 14838-14843. [PMID: 11815627]
2. Lambert, D.W., Hooper, N.M. and Turner, A.J. Angiotensin-converting enzyme 2 and new insights into the renin-angiotensin system. Biochem. Pharmacol. 75 (2008) 781-786. [PMID: 17897633]
3. Towler, P., Staker, B., Prasad, S.G., Menon, S., Tang, J., Parsons, T., Ryan, D., Fisher, M., Williams, D., Dales, N.A., Patane, M.A. and Pantoliano, M.W. ACE2 X-ray structures reveal a large hinge-bending motion important for inhibitor binding and catalysis. J. Biol. Chem. 279 (2004) 17996-18007. [PMID: 14754895]
Accepted name: tubulin-glutamate carboxypeptidase
Reaction: This is a subfamily of enzymes that cleave C-terminal and/or side chain amino acids from tubulins. The dual-specificity enzymes can cleave both α- and γ-linked L-glutamate from tubulins, removing the posttranslationally added polyglutamyl side chains from the C-terminal regions. In addition, the enzyme removes two glutamate residues from the C-terminus of β-tubulin and detyrosinated α-tubulin (from which the C-terminal L-tyrosine has been removed by EC 3.4.17.17, tubulinyl-Tyr carboxypeptidase). The latter is cleaved to δ2-tubulin and further to δ3-tubulin.
Other name(s): cytosolic carboxypeptidase 5; CCP5; Agtpbp1 (gene name); AGBL5 (gene name)
Links to other databases: BRENDA, EXPASY, KEGG, MEROPS, MetaCyc, CAS registry number:
References:
1. Rogowski, K., van Dijk, J., Magiera, M.M., Bosc, C., Deloulme, J.C., Bosson, A., Peris, L., Gold, N.D., Lacroix, B., Bosch Grau, M., Bec, N., Larroque, C., Desagher, S., Holzer, M., Andrieux, A., Moutin, M.J. and Janke, C. A family of protein-deglutamylating enzymes associated with neurodegeneration. Cell 143 (2010) 564-578. [PMID: 21074048]
2. Kimura, Y., Kurabe, N., Ikegami, K., Tsutsumi, K., Konishi, Y., Kaplan, O.I., Kunitomo, H., Iino, Y., Blacque, O.E. and Setou, M. Identification of tubulin deglutamylase among Caenorhabditis elegans and mammalian cytosolic carboxypeptidases (CCPs). J. Biol. Chem. 285 (2010) 22936-22941. [PMID: 20519502]
3. Pathak, N., Austin-Tse, C.A., Liu, Y., Vasilyev, A. and Drummond, I.A. Cytoplasmic carboxypeptidase 5 regulates tubulin glutamylation and zebrafish cilia formation and function. Mol. Biol. Cell 25 (2014) 1836-1844. [PMID: 24743595]
Accepted name: glutathione-S-conjugate glycine hydrolase
Reaction: a glutathione-S-conjugate + H2O = a [γ-glutamyl-L-cysteine]-S-conjugate + glycine
Other name(s): PCS1 (gene name); PRC1 (gene name); CPC (gene name); ATG42 (gene name); alr0975 (locus name)
Systematic name: glutathione-S-conjugate glycine hydrolase
Comments: The enzyme participates in a glutathione-mediated detoxification pathway found in plants, algae, fungi, and some bacteria. The enzymes from the plant Arabidopsis thaliana and the yeast Saccharomyces cerevisiae also catalyse the activity of EC 2.3.2.15, glutathione γ-glutamylcysteinyltransferase (phytochelatin synthase).
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:
References:
1. Beck, A., Lendzian, K., Oven, M., Christmann, A. and Grill, E. Phytochelatin synthase catalyzes key step in turnover of glutathione conjugates. Phytochemistry 62 (2003) 423-431. [PMID: 12620355]
2. Grzam, A., Tennstedt, P., Clemens, S., Hell, R. and Meyer, A.J. Vacuolar sequestration of glutathione S-conjugates outcompetes a possible degradation of the glutathione moiety by phytochelatin synthase. FEBS Lett. 580 (2006) 6384-6390. [PMID: 17097087]
3. Harada, E., von Roepenack-Lahaye, E. and Clemens, S. A cyanobacterial protein with similarity to phytochelatin synthases catalyzes the conversion of glutathione to γ-glutamylcysteine and lacks phytochelatin synthase activity. Phytochemistry 65 (2004) 3179-3185. [PMID: 15561184]
4. Tsuji, N., Nishikori, S., Iwabe, O., Shiraki, K., Miyasaka, H., Takagi, M., Hirata, K. and Miyamoto, K. Characterization of phytochelatin synthase-like protein encoded by alr0975 from a prokaryote, Nostoc sp. PCC 7120. Biochem. Biophys. Res. Commun. 315 (2004) 751-755. [PMID: 14975765]
5. Vivares, D., Arnoux, P. and Pignol, D. A papain-like enzyme at work: native and acyl-enzyme intermediate structures in phytochelatin synthesis. Proc. Natl. Acad. Sci. USA 102 (2005) 18848-18853. [PMID: 16339904]
6. Wunschmann, J., Krajewski, M., Letzel, T., Huber, E.M., Ehrmann, A., Grill, E. and Lendzian, K.J. Dissection of glutathione conjugate turnover in yeast. Phytochemistry 71 (2010) 54-61. [PMID: 19897216]
Contents
Accepted name: cathepsin X
Reaction: Release of C-terminal amino acid residues with broad specificity, but lacks action on C-terminal proline. Shows weak endopeptidase activity
Other names: cathepsin B2; cysteine-type carboxypeptidase; cathepsin IV; cathepsin Z; acid carboxypeptidase; lysosomal carboxypeptidase B
Comments: Cathepsin X is a lysosomal cysteine peptidase of family C1 (papain family). The pH optimum is dependent on the substrate and is 5.0 for the carboxypeptidase activity. Unstable above pH 7.0. Compound E-64, leupeptin and antipain are inhibitors, but not cystatin C. Cathepsin X is ubiquitously distributed in mammalian tissues. The propeptide is extremely short (38 amino acid residues) and the proenzyme is catalytically active. Human gene locus: 20q13. Formerly EC 3.4.18.1, cysteine-type carboxypeptidase
Links to other databases: BRENDA, EXPASY, KEGG, MEROPS, Metacyc, PDB, CAS registry number: 37217-21-3
References
1. Nägler, D.K., Zhang, R., Tam, W., Sulea, T., Purisima, E.O., and Ménard, R. Human cathepsin X: A cysteine protease with unique carboxypeptidase activity. Biochemistry 38 (1999) 12648-12654. [PMID: 9642240]
2. Nägler, D.K. and Ménard, R. Human cathepsin X: A novel cysteine protease of the papain family with a very short proregion and unique insertions. FEBS Lett. 434 (1998) 135-139. [PMID: 9738465]
3. Santamaría, I. Velasco, G., Pendás, A.M., Fueyo, A. and López-Otín, C. Cathepsin Z, a novel human cysteine proteinase with a short propeptide domain and a unique chromosomal location. J. Biol. Chem. 273 (1998) 16816-16823. [PMID: 9642240]
4. McDonald J.K. and Ellis, S. On the substrate specificity of cathepsins B1 and B2 including a new fluorogenic substrate for cathepsin B1. Life Sci. 17 (1975) 1269-1276. [PMID: 577]
5. Otto, K. and Riesenkönig H. Improved purification of cathepsin B1 and cathepsin B2. Biochim. Biophys. Acta 379 (1975) 462-475. [PMID: 1122298]
6. Ninjoor, V., Taylor, S.L. and Tappel, A.L. Purification and characterization of rat liver lysosomal cathepsin B2. Biochim. Biophys. Acta 370 (1974) 308-321. [PMID: 4429705]
Contents
EC 3.4.19.1 acylaminoacyl-peptidase
EC 3.4.19.2 peptidyl-glycinamidase
EC 3.4.19.3 pyroglutamyl-peptidase I
EC 3.4.19.4 deleted
EC 3.4.19.5 β-aspartyl-peptidase
EC 3.4.19.6 pyroglutamyl-peptidase II
EC 3.4.19.7 N-formylmethionyl-peptidase
EC 3.4.19.8 now EC 3.4.17.21
EC 3.4.19.9 folate γ-glutamyl hydrolase
EC 3.4.19.10 now EC 3.5.1.28
EC 3.4.19.11 γ-D-glutamyl-meso-diaminopimelate peptidase
EC 3.4.19.12 ubiquitinyl hydrolase 1
EC 3.4.19.13 glutathione γ-glutamate hydrolase
EC 3.4.19.14 leukotriene-C4 hydrolase
EC 3.4.19.15 desampylase
EC 3.4.19.16 glucosinolate γ-glutamyl hydrolase
Accepted name: acylaminoacyl-peptidase
Reaction: (1) cleavage of an N-acetyl or N-formyl amino acid from the N-terminus of a polypeptide
(2) internal cleavage of oxidized and glycated proteins
Other name(s): acylamino-acid-releasing enzyme; N-acylpeptide hydrolase; N-formylmethionine (fMet) aminopeptidase; α-N-acylpeptide hydrolase; oxidized protein hydrolase; acylpeptide hydrolase; AARE; AAP; OPH; AAH; APEH; ACPH
Comments: This is a bifunctional serine protease that has exopeptidase activity against Nα-acylated peptides and endopeptidase activity against oxidized and glycated proteins. In its exopeptidase mode the enzyme cleaves an N-acetyl or N-formyl amino acid from the N-terminus of a polypeptide. This class of enzymes is evolutionary deeply conserved and is found in bacteria, archaea, animals and plants with different quartenary structures. In humans, malfunction is linked to different types of cancer and sarcoma cell viability. In peptidase family S9 (prolyl oligopeptidase family).
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, MEROPS, PDB, CAS registry number: 73562-30-8
References:
1. Tsunazawa, S., Narita, K. and Ogata, K. Acylamino acid-releasing enzyme from rat liver. J. Biochem. (Tokyo) 77 (1975) 89-102. [PMID: 1137989]
2. Fujino, T., Watanabe, K., Beppu, M., Kikugawa, K. and Yasuda, H. Identification of oxidized protein hydrolase of human erythrocytes as acylpeptide hydrolase. Biochim. Biophys Acta 1478 (2000) 102-112. [PMID: 10719179]
3. Yamauchi, Y., Ejiri, Y., Toyoda, Y. and Tanaka, K. Identification and biochemical characterization of plant acylamino acid-releasing enzyme. J. Biochem. 134 (2003) 251-257. [PMID: 12966075]
4. Bartlam, M., Wang, G., Yang, H., Gao, R., Zhao, X., Xie, G., Cao, S., Feng, Y. and Rao, Z. Crystal structure of an acylpeptide hydrolase/esterase from Aeropyrum pernix K1. Structure 12 (2004) 1481-1488. [PMID: 15296741]
5. Shimizu, K., Kiuchi, Y., Ando, K., Hayakawa, M. and Kikugawa, K. Coordination of oxidized protein hydrolase and the proteasome in the clearance of cytotoxic denatured proteins. Biochem Biophys Res Commun 324 (2004) 140-146. [PMID: 15464994]
6. Nakai, A., Yamauchi, Y., Sumi, S. and Tanaka, K. Role of acylamino acid-releasing enzyme/oxidized protein hydrolase in sustaining homeostasis of the cytoplasmic antioxidative system. Planta 236 (2012) 427-436. [PMID: 22398639]
7. Gogliettino, M., Cocca, E., Sandomenico, A., Gratino, L., Iaccarino, E., Calvanese, L., Rossi, M. and Palmieri, G. Selective inhibition of acylpeptide hydrolase in SAOS-2 osteosarcoma cells: is this enzyme a viable anticancer target. Mol. Biol. Rep. 48 (2021) 1505-1519. [PMID: 33471263]
8. Kiss-Szeman, A.J., Straner, P., Jakli, I., Hosogi, N., Harmat, V., Menyhard, D.K. and Perczel, A. Cryo-EM structure of acylpeptide hydrolase reveals substrate selection by multimerization and a multi-state serine-protease triad. Chem. Sci. 13 (2022) 7132-7142. [PMID: 35799812]
Accepted name: peptidyl-glycinamidase
Reaction: Cleavage of C-terminal glycinamide from polypeptides
Other names: carboxyamidase; peptidyl carboxy-amidase; peptidyl-aminoacylamidase; carboxamidopeptidase; peptidyl amino acid amide hydrolase
Comments: Inactivates vasopressin and oxytocin by splitting off glycinamide. Also cleaves ester substrates of trypsin and chymotrypsin. Although glycinamide is by far the preferred leaving group, other aminoacylamides may also be released, e.g. phenylalaninamide. The toad skin enzyme is inhibited by diisopropyl fluorophosphate. Formerly EC 3.4.15.2
Links to other databases: BRENDA, EXPASY, KEGG, MEROPS, Metacyc, CAS registry number: 94047-14-0
References
1. Fruhaufová, L., Suska-Brezezinska, E., Barth, T. and Rychlik, I. Rat liver enzyme inactivating oxytocin and its deamino-carba analogues. Coll. Czech. Chem. Commun. 38 (1973) 2793-2798
2. Nardacci, N.J., Mukhopadhyay, S. and Campbell, B.J. Partial purification and characterization of the antidiuretic hormone in toad bladder. Biochim. Biophys. Acta 377 (1975) 146-157. [PMID: 1122284]
3. Simmons, W.H. and Walter, R. Carboxamidopeptidase: purificaction and characterization of a neurohypophyseal hormone inactivating peptidase from toad skin. Biochemistry 19 (1980) 39-48. [PMID: 6766314]
Accepted name: pyroglutamyl-peptidase I
Reaction: Release of an N-terminal pyroglutamyl group from a polypeptide, the second amino acid generally not being Pro
Other names: 5-oxoprolyl-peptidase; pyrase; pyroglutamate aminopeptidase; pyroglutamyl aminopeptidase; L-pyroglutamyl peptide hydrolase; pyrrolidone-carboxyl peptidase; pyrrolidone-carboxylate peptidase; pyrrolidonyl peptidase; L-pyrrolidonecarboxylate peptidase; pyroglutamidase; pyrrolidonecarboxylyl peptidase
Comments: A cysteine peptidase, known from bacteria, plants and animals. The enzyme from bacterial sources is used in protein sequencing, and is the type example of peptidase family C15. Formerly EC 3.4.11.8
Links to other databases: BRENDA, EXPASY, KEGG, MEROPS, Metacyc, PDB, CAS registry number: 9075-21-2
References
1. Tsuru, D., Nakamura, K., Yoshimoto, T. and Fujiwara, K. Pyroglutamyl-peptidase from Bacillus amyloliquefaciens. An improved purification method and some properties of the enzyme. Biochim. Biophys. Acta 791 (1984) 117-122
2. Awadé, A.C., Cleuziat, P., Gonzalès, T. and Robert-Baudouy, J. Pyrrolidone carboxyl peptidase (Pcp): an enzyme that removes pyroglutamic acid (pGlu) from pGlu-peptides and pGlu-proteins. Proteins: Struct. Funct. Genet. 20 (1994) 34-51. [PMID: 7824521]
3. Patti, J.M., Schneider, A., Garza, N. and Boles, J.O. Isolation and characterization of pcp, a gene encoding a pyrrolidone carboxyl peptidase in Staphylococcus aureus. Gene 166 (1995) 95-99. [PMID: 8529900]
4. Le Saux, O., Gonzalès, T. and Robert-Baudouy, J. Mutational analysis of the active site of Pseudomonas fluorescens pyrrolidone carboxyl peptidase. J. Bacteriol. 178 (1996) 3308-3313. [PMID: 8655512]
[EC 3.4.19.4 Deleted entry: N-Acetylmethionylpeptide peptidase (EC 3.4.19.4 created 1989, deleted 1992)]
Accepted name: β-aspartyl-peptidase
Reaction: Cleavage of a β-linked Asp residue from the N-terminus of a polypeptide
Other name(s): β-aspartyl dipeptidase; β-aspartyl peptidase; β-aspartyldipeptidase
Comments: Other isopeptide bonds, e.g. γ-glutamyl and β-alanyl, are not hydrolysed. A mammalian, cytosolic enzyme. Formerly EC 3.4.13.10
Links to other databases: BRENDA, EXPASY KEGG, Metacyc, PDB, CAS registry number: 37288-74-7
References
1. Haley, E.E. β-Aspartyl peptidase from rat liver. Methods Enzymol. 19 (1970) 737-741
Accepted name: pyroglutamyl-peptidase II
Reaction: Release of the N-terminal pyroglutamyl group from pGluHis-Xaa tripeptides and pGluHis-Xaa-Gly tetrapeptides
Other names: thyroliberinase; pyroglutamyl aminopeptidase II; thyrotropin-releasing factor pyroglutamate aminopeptidase; pyroglutamate aminopeptidase II; pyroglutamyl peptidase II; thyroliberin-hydrolyzing pyroglutamate aminopeptidase; thyrotropin-releasing hormone-degrading pyroglutamate aminopeptidase; thyrotropin-releasing hormone-degrading peptidase; TRH aminopeptidase
Comments: Highly specific for thyrotropin releasing hormone (pyroglutamyl-histidyl-prolylamide). Will not cleave the pyroglutamyl-histidyl bond of luteinizing hormone releasing hormone. Found in serum and brain. Inhibited by metal chelators. In peptidase family M1 (membrane alanyl aminopeptidase family)
Links to other databases: BRENDA, EXPASY, MEROPS, Metacyc, CAS registry number: 60063-88-9
References
1. Bauer, K. and Nowak, P. Characterization of a thyroliberin-degrading serum enzyme catalyzing the hydrolysis of thyroliberin at the pyroglutamyl-histidine bond. Eur. J. Biochem. 99 (1979) 239-246. [PMID: 115687]
2. O'Connor, B. and O'Cuinn, G. Purification of and kinetic studies on a narrow specifity synaptosomal membrane pyroglutamate aminopeptidase from guinea-pig brain. Eur. J. Biochem. 150 (1985) 47-52. [PMID: 2862039]
3. Wilk, S. and Wilk, E.K. Pyroglutamyl peptidase II, a thyrotropin releasing hormone degrading enzyme: purification and specificity studies of the rabbit brain enzyme. Neurochem. Int. 15 (1989) 81-89
Accepted name: N-formylmethionyl-peptidase
Reaction: Release of an N-terminal, formyl-methionyl residue from a polypeptide
Other names: (fMet)-releasing enzyme; formylmethionine aminopeptidase
Comments: Highly specific for N-formylmethionyl peptides. Will not cleave methionyl peptides or N-formyl derivatives of amino acids other than methionine. Isolated from rat liver. Inhibited by heavy metals and activated by Cl-
Links to other databases: BRENDA, EXPASY, KEGG, MEROPS, Metacyc, CAS registry number: 76106-80-4
References
1. Suda, H., Yamamoto, K., Aoyagi, T. and Umezawa, H. Purification and properties of N-formylmethionine aminopeptidase from rat liver. Biochim. Biophys. Acta 616 (1980) 60-67. [PMID: 7437450]
[EC 3.4.19.8 Transferred entry: now EC 3.4.17.21 - glutamate carboxypeptidase II (EC 3.4.19.8 created 1992, deleted 2000)]
Accepted name: folate γ-glutamyl hydrolase
Reaction: tetrahydropteroyl-(γ-glutamyl)n + (n-1) H2O = 5,6,7,8-tetrahydrofolate + (n-1) L-glutamate
For diagram of reaction click here.
Other name(s): GGH (gene name) conjugase; folate conjugase; lysosomal γ-glutamyl carboxypeptidase; γ-Glu-X carboxypeptidase; pteroyl-poly-γ-glutamate hydrolase; carboxypeptidase G; folic acid conjugase; poly(γ-glutamic acid) endohydrolase; polyglutamate hydrolase; poly(glutamic acid) hydrolase II; pteroylpoly-γ-glutamyl hydrolase; γ-glutamyl hydrolase
Systematic name: tetrahydropteroyl-poly-γ-glutamyl γ-glutamyl hydrolase
Comments: The enzyme, which occurs only in animals and plants, can be either endo- and/or exopeptidase. It acts on tetrahydropteroyl polyglutamates and their modified forms, as well as the polyglutamates of the folate breakdown product N-(4-aminobenzoyl)-L-glutamate (pABA-Glu). The initial cleavage may release either monoglutamate or poly-γ-glutamate of two or more residues, depending on the specific enzyme. For example, GGH1 from the plant Arabidopsis thaliana cleaves pentaglutamates, mainly to di- and triglutamates, whereas GGH2 from the same organism yields mainly monoglutamates. The enzyme is lysosomal (and secreted) in animals and vacuolar in plants.
Links to other databases: BRENDA, EXPASY, ExplorEnz, GTD, KEGG, MetaCyc, MEROPS, PDB, CAS registry number: 9074-87-7
References:
1. McGuire, J.J. and Coward, J.K. Pteroylpolyglutamates: biosynthesis, degradation and function.. In: Blakley, R.L. and Benkovic, S.J. (Eds), Folates and Pterins, John Wiley and Sons, New York, 1984, pp. 135-191.
2. Wang, Y., Nimec, Z., Ryan, T.J., Dias, J.A. and Galivan, J. The properties of the secreted γ-glutamyl hydrolases from H35 hepatoma cells. Biochim. Biophys. Acta 1164 (1993) 227-235. [PMID: 8343522]
3. Yao, R., Rhee, M.S. and Galivan, J. Effects of γ-glutamyl hydrolase on folyl and antifolylpolyglutamates in cultured H35 hepatoma cells. Mol. Pharmacol. 48 (1995) 505-511. [PMID: 7565632]
4. Yao, R., Schneider, E., Ryan, T.J. and Galivan, J. Human γ-glutamyl hydrolase: cloning and characterization of the enzyme expressed in vitro. Proc. Natl. Acad. Sci. USA 93 (1996) 10134-10138. [PMID: 8816764]
5. Yao, R., Nimec, Z., Ryan, T.J. and Galivan, J. Identification, cloning, and sequencing of a cDNA coding for rat γ-glutamyl hydrolase. J. Biol. Chem. 271 (1996) 8525-8528. [PMID: 8621474]
6. Orsomando, G., de la Garza, R.D., Green, B.J., Peng, M., Rea, P.A., Ryan, T.J., Gregory, J.F., 3rd and Hanson, A.D. Plant γ-glutamyl hydrolases and folate polyglutamates: characterization, compartmentation, and co-occurrence in vacuoles. J. Biol. Chem. 280 (2005) 28877-28884. [PMID: 15961386]
7. Akhtar, T.A., McQuinn, R.P., Naponelli, V., Gregory, J.F., 3rd, Giovannoni, J.J. and Hanson, A.D. Tomato γ-glutamylhydrolases: expression, characterization, and evidence for heterodimer formation. Plant Physiol. 148 (2008) 775-785. [PMID: 18757550]
[EC 3.4.19.10 Transferred entry: now EC 3.5.1.28 - N-acetylmuramoyl-L-alanine amidase (EC 3.4.19.10 created 1972 as EC 3.4.12.5, transferred 1978 to EC 3.4.17.7, transferred 1992 to EC 3.4.19.10, deleted 1997)]
Accepted name: γ-D-glutamyl-meso-diaminopimelate peptidase
Reaction: Hydrolysis of γ-D-glutamyl bonds to the L-terminus (position 7) of meso-diaminopimelic acid (meso-A2pm) in 7-(L-Ala-γ-D-Glu)-meso-A2pm and 7-(L-Ala-γ-D-Glu)-7-(D-Ala)-meso-A2pm. It is required that the D-terminal amino and carboxy groups of meso-A2pm are unsubstituted
Other names: endopeptidase I; γ-D-glutamyldiaminopimelate endopeptidase; γ-D-glutamyl-L-meso-diaminopimelate peptidoglycan hydrolase; γ-glutamyl-L-meso-diaminopimelyl endopeptidase; γ-D-glutamyl-meso-diaminopimelate endopeptidase; γ-D-glutamyl-meso-diaminopimelic peptidoglycan hydrolase; γ-D-glutamyl-meso-diaminopimelic endopeptidase; γ-D-glutamyl-meso-D-aminopimelic endopeptidase
Comments: A 45-kDa metallopeptidase from Bacillus sphaericus, the substrates being components of the bacterial spore wall. A member of peptidase family M14 (carboxypeptidase A family). Endopeptidase II has similar activity, but differs in cellular location, molecular mass and catalytic mechanism [3]
Links to other databases: BRENDA, EXPASY, KEGG, MEROPS, Metacyc, PDB, CAS registry number: 62572-28-5
References
1. Arminjon, F., Guinand, M., Vacheron, M.-J. and Michel, G. Specificity profiles of the membrane-bound γ-D-glutamyl-(L)meso-diaminopimelate endopeptidase and LD-carboxypeptidase from Bacillus sphaericus 9602. Eur. J. Biochem. 73 (1977) 557-565. [PMID: 849747]
2. Garnier, M., Vacheron, M.-J., Guinard, M. and Michel, G. Purification and partial characterization of the extracellular γ-D-glutamyl-(L)meso-diaminopimelate endopeptidase I, from Bacillus sphaericus NCTC 9602. Eur. J. Biochem. 148 (1985) 539-543. [PMID: 3922755]
3. Hourdou, M.-L., Guinand, M., Vacheron, M.-J., Michel, G., Denoroy, L., Duez, C., Englebert, S., Joris, B., Weber, G. and Ghuysen, J.-M. Characterization of the sporulation-related γ-D-glutamyl-(L)meso-diaminopimelic-acid-hydrolysing peptidase I of Bacillus sphaericus NCTC 9602 as a member of the metallo(zinc) carboxypeptidase A family. Modular design of the protein. Biochem. J. 292 (1993) 563-570. [PMID: 8503890]
Accepted name: ubiquitinyl hydrolase 1
Reaction: Thiol-dependent hydrolysis of ester, thioester, amide, peptide and isopeptide bonds formed by the C-terminal Gly of ubiquitin (a 76-residue protein attached to proteins as an intracellular targeting signal)
Other names: ubiquitin C-terminal hydrolase; yeast ubiquitin hydrolase
Comments: Links to polypeptides smaller than 60 residues are hydrolysed more readily than those to larger polypeptides. Isoforms exist with quantitatively different specificities, amongst the best known being UCH-L1 and UCH-L3, which are major proteins of the brain of mammals [1]. Inhibited by ubiquitin aldehyde (in which Gly76 is replaced by aminoacetaldehyde). Ubiquitinyl hydrolase 1 is the type example of peptidase family C12, with a similar protein fold to papain and catalytic amino acids Cys, His and Asp. There is a separate family (C19) of enzymes that also hydrolyse ubiquitinyl bonds, and it is thought that all the ubiquitinyl hydrolases are also ubiquitin thiolesterases (EC 3.1.2.15)
Links to other databases: BRENDA, EXPASY, KEGG, MEROPS, Metacyc, PDB, CAS registry number: 86480-67-3 and 189642-63-5
References
1. Johnston, S.C., Larsen, C.N., Cook, W.J., Wilkinson, K.D. and Hill, C.P. Crystal structure of a deubiquitinating enzyme (human UCH-L3) at 1.8Å resolution.EMBO J. 16 (1997) 3787-3796. [PMID: 9233788]
2. Wilkinson, K.D. Ubiquitin C-terminal hydrolase. In: Handbook of Proteolytic Enzymes, (Barrett, A.J., Rawlings, N.D. and Woessner, J.F. eds), pp. 470-472 (1998) Academic Press, London
Accepted name: glutathione γ-glutamate hydrolase
Reaction: (1) glutathione + H2O = L-cysteinylglycine + L-glutamate
(2) a glutathione-S-conjugate + H2O = an (L-cysteinylglycine)-S-conjugate + L-glutamate
Other name(s): glutathionase; γ-glutamyltranspeptidase (ambiguous); glutathione hydrolase; GGT (gene name); ECM38 (gene name)
Comments: This is a bifunctional protein that also has the activity of EC 2.3.2.2, γ-glutamyltransferase. The enzyme binds its substrate by forming an initial γ-glutamyl-enzyme intermediate, releasing the L-cysteinylglycine part of the molecule. The enzyme then reacts with either a water molecule or a different acceptor substrate (usually an L-amino acid or a dipeptide) to form L-glutamate or a product containing a new γ-glutamyl isopeptide bond, respectively. The enzyme acts on glutathione, glutathione-S-conjugates, and, at a lower level, on other substrates with an N-terminal L-γ-glutamyl residue. It plays a crucial part in the glutathione-mediated xenobiotic detoxification pathway. The enzyme consists of two chains that are created by the proteolytic cleavage of a single precursor polypeptide.
Links to other databases: BRENDA, EXPASY, ExplorEnz, KEGG, MetaCyc, PDB, CAS registry number:
References:
1. Hanigan, M.H. and Ricketts, W.A. Extracellular glutathione is a source of cysteine for cells that express γ-glutamyl transpeptidase. Biochemistry 32 (1993) 6302-6306. [PMID: 8099811]
2. Carter, B.Z., Wiseman, A.L., Orkiszewski, R., Ballard, K.D., Ou, C.N. and Lieberman, M.W. Metabolism of leukotriene C4 in γ-glutamyl transpeptidase-deficient mice. J. Biol. Chem. 272 (1997) 12305-12310. [PMID: 9139674]
3. Suzuki, H. and Kumagai, H. Autocatalytic processing of γ-glutamyltranspeptidase. J. Biol. Chem. 277 (2002) 43536-43543. [PMID: 12207027]
4. Okada, T., Suzuki, H., Wada, K., Kumagai, H. and Fukuyama, K. Crystal structures of γ-glutamyltranspeptidase from Escherichia coli, a key enzyme in glutathione metabolism, and its reaction intermediate. Proc. Natl. Acad. Sci. USA 103 (2006) 6471-6476. [PMID: 16618936]
5. Boanca, G., Sand, A., Okada, T., Suzuki, H., Kumagai, H., Fukuyama, K. and Barycki, J.J. Autoprocessing of Helicobacter pylori γ-glutamyltranspeptidase leads to the formation of a threonine-threonine catalytic dyad. J. Biol. Chem. 282 (2007) 534-541. [PMID: 17107958]
6. Okada, T., Suzuki, H., Wada, K., Kumagai, H. and Fukuyama, K. Crystal structure of the γ-glutamyltranspeptidase precursor protein from Escherichia coli. Structural changes upon autocatalytic processing and implications for the maturation mechanism. J. Biol. Chem. 282 (2007) 2433-2439. [PMID: 17135273]
7. Grzam, A., Martin, M.N., Hell, R. and Meyer, A.J. γ-Glutamyl transpeptidase GGT4 initiates vacuolar degradation of glutathione S-conjugates in Arabidopsis. FEBS Lett. 581 (2007) 3131-3138. [PMID: 17561001]
8. Wickham, S., West, M.B., Cook, P.F. and Hanigan, M.H. Gamma-glutamyl compounds: substrate specificity of γ-glutamyl transpeptidase enzymes. Anal. Biochem. 414 (2011) 208-214. [PMID: 21447318]
9. Keillor, J.W., Castonguay, R. and Lherbet, C. Gamma-glutamyl transpeptidase substrate specificity and catalytic mechanism. Methods Enzymol. 401 (2005) 449-467. [PMID: 16399402]
Accepted name: leukotriene-C4 hydrolase
Reaction: leukotriene C4 + H2O = leukotriene D4 + L-glutamate
Other name(s): γ-glutamyl leukotrienase; GGT5
Comments: The mouse enzyme is specific for leukotriene C4, while the human enzyme also has considerable activity towards glutathione and oxidized glutathione (cf. EC 3.4.19.13, glutathione hydrolase) [3-4].
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, PDB, CAS registry number:
References:
1. Carter, B.Z., Wiseman, A.L., Orkiszewski, R., Ballard, K.D., Ou, C.N. and Lieberman, M.W. Metabolism of leukotriene C4 in γ-glutamyl transpeptidase-deficient mice. J. Biol. Chem. 272 (1997) 12305-12310. [PMID: 9139674]
2. Shi, Z.Z., Han, B., Habib, G.M., Matzuk, M.M. and Lieberman, M.W. Disruption of γ-glutamyl leukotrienase results in disruption of leukotriene D4 synthesis in vivo and attenuation of the acute inflammatory response. Mol. Cell Biol. 21 (2001) 5389-5395. [PMID: 11463821]
3. Han, B., Luo, G., Shi, Z.Z., Barrios, R., Atwood, D., Liu, W., Habib, G.M., Sifers, R.N., Corry, D.B. and Lieberman, M.W. γ-glutamyl leukotrienase, a novel endothelial membrane protein, is specifically responsible for leukotriene D4 formation in vivo. Am J Pathol 161 (2002) 481-490. [PMID: 12163373]
4. Wickham, S., West, M.B., Cook, P.F. and Hanigan, M.H. Gamma-glutamyl compounds: substrate specificity of γ-glutamyl transpeptidase enzymes. Anal. Biochem. 414 (2011) 208-214. [PMID: 21447318]
Accepted name: desampylase
Reaction: an N6-[small archaeal modifier protein]-[protein]-L-lysine + H2O = a [protein]-L-lysine + a small archaeal modifier protein
Glossary: SAMP = small archaeal modifier protein
Other name(s): SAMP-protein conjugate cleaving protease; HvJAMM1
Systematic name: N6-[small archaeal modifier protein]-[protein]-L-lysine hydrolase
Comments: The enzyme, characterized from the archaeon Haloferax volcanii, specifically cleaves the ubiquitin-like small modifier proteins SAMP1 and SAMP2 from protein conjugates, hydrolysing the isopeptide bond between a lysine residue of the target protein and the C-terminal glycine of the modifier protein. The enzyme contains Zn2+. cf. EC 3.4.19.12, ubiquitinyl hydrolase 1. In peptidase family M67.
Links to other databases: BRENDA, EXPASY, KEGG, MEROPS, Metacyc, PDB, CAS registry number:
References:
1. Hepowit, N.L., Uthandi, S., Miranda, H.V., Toniutti, M., Prunetti, L., Olivarez, O., De Vera, I.M., Fanucci, G.E., Chen, S. and Maupin-Furlow, J.A. Archaeal JAB1/MPN/MOV34 metalloenzyme (HvJAMM1) cleaves ubiquitin-like small archaeal modifier proteins (SAMPs) from protein-conjugates. Mol. Microbiol. 86 (2012) 971-987. [PMID: 22970855]
Accepted name: glucosinolate γ-glutamyl hydrolase
Reaction: (1) an (E)-1-(glutathion-S-yl)-N-hydroxy-ω-(methylsulfanyl)alkan-1-imine + H2O = an (E)-1-(L-cysteinylglycin-S-yl)-N-hydroxy-ω-(methylsulfanyl)alkan-1-imine + L-glutamate
(2) (E)-1-(glutathion-S-yl)-N-hydroxy-2-(1H-indol-3-yl)ethan-1-imine + H2O = (E)-1-(L-cysteinylglycin-S-yl)-N-hydroxy-2-(1H-indol-3-yl)ethan-1-imine + L-glutamate
(3) (glutathion-S-yl)(1H-indol-3-yl)acetonitrile + H2O = (L-cysteinylglycin-S-yl)(1H-indol-3-yl)acetonitrile + L-glutamate
(4) (Z)-1-(glutathion-S-yl)-N-hydroxy-2-phenylethan-1-imine + H2O = (Z)-1-(L-cysteinyglycin-S-yl)-N-hydroxy-2-phenylethan-1-imine + L-glutamate
Other name(s): GGP1 (gene name); GGP3 (gene name)
Comments: This enzyme, characterized from the plant Arabidopsis thaliana, participates in the biosynthesis of the plant defense compounds glucosinolates and camalexin. It is the only known plant enzyme capable of hydrolysing the γ-glutamyl residue of glutathione in the cytosol.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:
References:
1. Geu-Flores, F., Møldrup, M.E., Böttcher, C., Olsen, C.E., Scheel, D. and Halkier, B.A. Cytosolic γ-glutamyl peptidases process glutathione conjugates in the biosynthesis of glucosinolates and camalexin in Arabidopsis. Plant Cell 23 (2011) 2456-2469. [PMID: 21712415]