Yaa-, in which Xaa is preferably Leu, but may be other amino acids including Pro although not Arg or Lys, and Yaa may be Pro. Amino acid amides and methyl esters are also readily hydrolysed, but rates on arylamides are exceedingly lowContinued from Transferred entries
EC 3.4.11 Aminopeptidases
EC 3.4.13 Dipeptidases
EC 3.4.14 Dipeptidyl-peptidases and tripeptidyl-peptidases
EC 3.4.15 Peptidyl-Dipeptidases
Contents
EC 3.4.11.1 leucyl aminopeptidase
EC 3.4.11.2 membrane alanyl aminopeptidase
EC 3.4.11.3 cystinyl aminopeptidase
EC 3.4.11.4 tripeptide aminopeptidase
EC 3.4.11.5 prolyl aminopeptidase
EC 3.4.11.6 aminopeptidase B
EC 3.4.11.7 glutamyl aminopeptidase
EC 3.4.11.8 now EC 3.4.19.3
EC 3.4.11.9 Xaa-Pro aminopeptidase
EC 3.4.11.10 bacterial leucyl aminopeptidase
EC 3.4.11.11 deleted
EC 3.4.11.12 deleted (Supplement 4)
EC 3.4.11.13 clostridial aminopeptidase
EC 3.4.11.14 cytosol alanyl aminopeptidase
EC 3.4.11.15 aminopeptidase Y
EC 3.4.11.16 Xaa-Trp aminopeptidase
EC 3.4.11.17 tryptophanyl aminopeptidase
EC 3.4.11.18 methionyl aminopeptidase
EC 3.4.11.19 D-stereospecific aminopeptidase
EC 3.4.11.20 aminopeptidase Ey
EC 3.4.11.21 aspartyl aminopeptidase
EC 3.4.11.22 aminopeptidase I
EC 3.4.11.23 pepB aminopeptidase
EC 3.4.11.24 aminopeptidase S
EC 3.4.11.25 β-peptidyl aminopeptidase
EC 3.4.11.26 intermediate cleaving peptidase 55
EC 3.4.11.27 archaeal arginyl aminopeptidase
Accepted name: leucyl aminopeptidase
Reaction: Release of an N-terminal amino acid, XaaYaa-, in which Xaa is preferably Leu, but may be other amino acids including Pro although not Arg or Lys, and Yaa may be Pro. Amino acid amides and methyl esters are also readily hydrolysed, but rates on arylamides are exceedingly low
Other names: leucine aminopeptidase; leucyl peptidase; peptidase S; cytosol aminopeptidase; cathepsin III; L-leucine aminopeptidase; leucinaminopeptidase; leucinamide aminopeptidase; FTBL proteins; proteinates FTBL; aminopeptidase II; aminopeptidase III; aminopeptidase I
Comments: A zinc enzyme isolated from pig kidney and cattle lens; activated by heavy metal ions. Type example of peptidase family M17. Formerly EC 3.4.1.1
Links to other databases: BRENDA, EXPASY, GTD, KEGG, MEROPS, Metacyc, PDB, CAS registry number: 9001-61-0
References
1. Himmelhoch, S.R. Leucine aminopeptidase from swine kidney. Methods Enzymol. 19 (1970) 508-513
2. Delange, R.J. and Smith, E.L. Leucine aminopeptidase and other N-terminal exopeptidases. In The Enzymes, 3rd edn (Boyer, P.D. ed.), vol 3, pp. 81-118 (1971) Academic Press, New York
3. van Loon-Klaasen, L.A.H., Cuypers, H.T., van Westreenen, H., de Jong, W.W. and Bloemendal, H. The primary structure of bovine lens leucine aminopeptidase. Complete amino acid sequence of the N-terminal cyanogen bromide fragment and site limited tryptic digestion. Biochem. Biophys. Res. Commun. 95 (1980) 334-341. [PMID: 7417261]
Accepted name: membrane alanyl aminopeptidase
Reaction: Release of an N-terminal amino acid, XaaYaa- from a peptide, amide or arylamide. Xaa is preferably Ala, but may be most amino acids including Pro (slow action). When a terminal hydrophobic residue is followed by a prolyl residue, the two may be released as an intact Xaa-Pro dipeptide
Other names: microsomal aminopeptidase; aminopeptidase M; aminopeptidase N; particle-bound aminopeptidase; amino-oligopeptidase; alanine aminopeptidase; membrane aminopeptidase I; pseudo leucine aminopeptidase; alanyl aminopeptidase; alanine-specific aminopeptidase; cysteinylglycine dipeptidase; cysteinylglycinase; L-alanine aminopeptidase; CD13
Comments: A zinc enzyme, not activated by heavy metal ions. Type example of peptidase family M1. Formerly EC 3.4.1.2
Links to other databases: BRENDA, EXPASY, KEGG, MEROPS, Metacyc, PDB, CAS registry number: 9054-63-1
References
1. Wachsmuth, D., Fritze, I. and Pfleiderer, G. An aminopeptidase occurring in pig kidney. I. An improved method of preparation. Physical and enzymatic properties. Biochemistry 5 (1966) 169-174. [PMID: 5938934]
2. Kim, Y.S. and Brophy, E.J. Rat intestinal brush border membrane peptidases. I. Solubilization, purification of two different forms of enzyme. J. Biol. Chem. 251 (1976) 3199-3205. [PMID: 931983]
3. Gray, G.M. and Santiago, N.A. Intestinal surface amino-oligopeptidases. I. Isolation of two weight isomers and their subunits from rat brush border. J. Biol. Chem. 252 (1977) 4922-4928. [PMID: 873921]
4. Sjöström, H., Norén, O., Jeppesen, L., Staun, M., Svensson, B. and Christiansen, L. Purification of different amphiphilic forms of a microvillus aminopeptidase from pig small intestine using immunoadsorbent chromatography. Eur. J. Biochem. 88 (1978) 503-511. [PMID: 357150]
5. Ferracci, H. and Maroux, S. Rabbit intestinal aminopeptidase N. Purification and molecular properties. Biochim. Biophys. Acta. 599 (1980) 448-463. [PMID: 6105876]
Accepted name: cystinyl aminopeptidase
Reaction: Release of an N-terminal amino acid, CysXaa-, in which the half-cystine residue is involved in a disulfide loop, notably in oxytocin or vasopressin. Hydrolysis rates on a range of aminoacyl arylamides exceed that for the cystinyl derivative, however [4]
Other names: cystyl-aminopeptidase; oxytocinase; cystine aminopeptidase; L-cystine aminopeptidase; oxytocin peptidase; vasopresssinase
Comments: A zinc-containing sialoglycoprotein In peptidase family M1 (membrane alanyl aminopeptidase family)
Links to other databases: BRENDA, EXPASY, KEGG, MEROPS, Metacyc, CAS registry number: 9031-41-8
References
1. Sjöholm, I. Biochemical studies on oxytocin and oxytocinase. Acta Pharm. Suec. 4 (1967) 81-96. [PMID: 6041057]
2. Sjöholm, I. and Yman, L. Degradation of oxytocin, lysine vasopressin, angiotensin II, and angiotensin II amide by oxytocinase (cystine aminopeptidase). Acta Pharm. Suec. 4 (1967) 65-76. [PMID: 4292447]
3. Yman, L. Studies on human serum aminopeptidase. Some properties of oxytocinase, human serum aminopeptidase A and leucine aminopeptidase and their purification from retroplacental serum. Acta Pharm. Suec. 7 (1970) 75-86. [PMID: 5421622]
4. Sakura, H., Lin, T.Y., Doi, M., Mizutani, S. and Kawashima, Y. Purification and properties of oxytocinase, a metalloenzyme. Biochem. Int. 2 (1981) 173-179
Accepted name: tripeptide aminopeptidase
Reaction: Release of the N-terminal residue from a tripeptide
Other names: tripeptidase; aminotripeptidase; aminoexotripeptidase; lymphopeptidase; imidoendopeptidase; peptidase B; alanine-phenylalanine-proline arylamidase; peptidase T
Comments: A zinc enzyme, widely distributed in mammalian tissues. Formerly EC 3.4.1.3
Links to other databases: BRENDA, EXPASY, KEGG, MEROPS, Metacyc, PDB, CAS registry number: 9056-26-2
References
1. Doumeng, C. and Maroux, S. Aminopeptidase, a cytosol enzyme from rabbit intestinal mucosa. Biochem. J. 177 (1979) 801-808. [PMID: 109082]
2. Sachs, L. and Marks, N. A highly specific aminotripeptidase of rat brain cytosol. Substrate specifity and effects of inhibitors. Biochim. Biophys. Acta 706 (1982) 229-238. [PMID: 7126601]
Accepted name: prolyl aminopeptidase
Reaction: Release of N-terminal proline from a peptide
Other names: proline aminopeptidase; Pro-X aminopeptidase; cytosol aminopeptidase V; proline iminopeptidase
Comments: A Mn2+-requiring enzyme present in the cytosol of mammalian and microbial cells. In contrast to the mammalian form, the bacterial form of the enzyme (type example of peptidase family S33) hydrolyses both polyproline and prolyl-2-naphthylamide. The mammalian enzyme, which is not specific for prolyl bonds, is possibly identical with EC 3.4.11.1, leucyl aminopeptidase."
Links to other databases: BRENDA, EXPASY, KEGG, MEROPS, Metacyc, PDB, CAS registry number: 9025-40-5
References
1. Sarid, S., Berger, A. and Katchalski, E. Proline iminopeptidase. II. Purification and comparison with iminopeptidase (prolinase). J. Biol. Chem. 237 (1962) 2207-2212
2. Nordwig, A. and Mayer, H. The cleavage of prolyl peptidases by kidney peptidases. Hoppe-Seyler's Z. Physiol. Chem. 354 (1973) 380-383. [PMID: 4803482]
3. Turzynski, A. and Mentlein, R. Prolyl aminopeptidase from rat brain and kidney. Action on peptides and identification as leucyl aminopeptidase. Eur. J. Biochem. 190 (1990) 509-515. [PMID: 2373079]
Accepted name: aminopeptidase B
Reaction: Release of N-terminal Arg and Lys from oligopeptides when P1' is not Pro. Also acts on arylamides of Arg and Lys
Glossary entries
amastatin = Leu[1ψ2,CHOHCONH]ValValAsp
arphamenine A = Arg[1ψ2,COCH2]Phe
arphamenine B = Arg[1ψ2,COCH2]Tyr
bestatin = Phe[1ψ2,CHOHCONH]Leu
Other names: arylamidase II; arginine aminopeptidase; arginyl aminopeptidase; Cl--activated arginine aminopeptidase; cytosol aminopeptidase IV; L-arginine aminopeptidase
Comments: Cytosolic or membrane-associated enzyme from mammalian tissues, activated by chloride ions and low concentrations of thiol compounds. This is one of the activities of the bifunctional enzyme EC 3.3.2.6, leukotriene-A4 hydrolase [5,6]. Potently inhibited by arphamenine B, and also inhibited by chelating agents, N-ethylmaleimide, arphamenine A, amastatin and bestatin. A zinc metallopeptidase in family family M1 (membrane alanyl aminopeptidase family) [4,5].
Links to other databases: BRENDA, EXPASY, KEGG, MEROPS, Metacyc, CAS registry number: 9073-92-1
References
1. Gainer, H., Russell, J.T. and Loh, Y.P. An aminopeptidase activity in bovine pituitary secretory vesicles that cleaves the N-terminal arginine from beta-lipotropin(60-65). FEBS Lett. 175 (1984) 135-139. [PMID: 6434344]
2. Belhacène, N., Mari, B., Rossi, B. and Auberger, P. Characterization and purification of T lymphocyte aminopeptidase B: a putative marker of T cell activation. Eur. J. Immunol. 23 (1993) 1948-1955. [PMID: 8344358]
3. Cadel, S., Pierotti, A.R., Foulon, T., Créminon, C., Barré, N., Segrétain, D. and Cohen, P. Aminopeptidase-B in the rat testes: Isolation, functional properties and cellular localization in the seminiferous tubules. Mol. Cell. Endocrinol. 110 (1995) 149-160. [PMID: 7672445]
4. Fukasawa, K.M., Fukasawa, K., Kanai, M., Fujii, S. and Harada, M. Molecular cloning and expression of rat liver aminopeptidase B. J. Biol. Chem. 271 (1996) 30731-30735. [PMID: 8940051]
5. Cadel, S., Foulon, T., Viron, A., Balogh, A., Midol-Monnet, S., Noel, N. and Cohen, P. Aminopeptidase B from the rat testis is a bifunctional enzyme structually related to leukotriene-A4 hydrolase. Proc. Natl. Acad. Sci. USA 94 (1997) 2963-2968. [PMID: 9096329]
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) 11269-112673. [PMID: 8157657]
Accepted name: glutamyl aminopeptidase
Reaction: Release of N-terminal glutamate (and to a lesser extent aspartate) from a peptide
Other names: aminopeptidase A; aspartate aminopeptidase; angiotensinase A; glutamyl peptidase; Ca2+-activated glutamate aminopeptidase; membrane aminopeptidase II; antigen BP-1/6C3 of mouse B lymphocytes; L-aspartate aminopeptidase; angiotensinase A2
Comments: Ca2+-activated and generally membrane-bound. A zinc-metallopeptidase In family M1 (membrane alanyl aminopeptidase family)
Links to other databases: BRENDA, EXPASY, KEGG, MEROPS, Metacyc, PDB, CAS registry number: 9074-83-3
References
1. Glenner, G.G., McMillan, P.J. and Folk, J.E. A mammalian peptidase specific for the hydrolysis of N-terminal α-L-glutamyl and aspartyl residues. Nature 194 (1962) 867 only
2. Chulkova, T.M. and Orekhovich, V.N. Isolation and properties of aminopeptidase A from bovine kidneys. Biokhimiya 43 (1978) 964-969. [PMID: 508862]
3. Danielsen, E.M., Norén, O., Sjöström, H., Ingram, J. and Kenny, J. Proteins of the kidney microvillar membrane. Aspartate aminopeptidase: purification by immunoadsorbent chromatography and properties of the detergent- and proteinase-solubilized forms. Biochem. J. 189 (1980) 591-603. [PMID: 7011318]
4. Tobe, H., Kojima, F., Aoyagi, T. and Umezawa, H. Purification by affinity chromatography using amastatin and properties of aminopeptidase A from pig kidney. Biochim. Biophys. Acta 613 (1980) 459-468. [PMID: 7448199]
5. Wu, Q., Lahti, J.M., Air, G.M., Burrows, P.D. and Cooper, M.D. Molecular cloning of the murine BP-1/6C3 antigen: a member of the zinc-dependent metallopeptidase family. Proc. Natl. Acad. Sci. USA 87 (1990) 993-997. [PMID: 1689065]
[EC 3.4.11.8 Transferred entry: now EC 3.4.19.3 - pyroglutamyl-peptidase I (EC 3.4.11.8 created 1972, deleted 1981)]
Accepted name: Xaa-Pro aminopeptidase
Reaction: Release of any N-terminal amino acid, including proline, that is linked to proline, even from a dipeptide or tripeptide
Other names: proline aminopeptidase; aminopeptidase P; aminoacylproline aminopeptidase; X-Pro aminopeptidase
Comments: A Mn2+-dependent, generally membrane-bound enzyme present in both mammalian and bacterial cells. In peptidase family M24 (methionyl aminopeptidase family)
Links to other databases: BRENDA, EXPASY, KEGG, MEROPS, Metacyc, PDB, CAS registry number: 37288-66-7
References
1. Yaron, A. and Mlynar, D. Aminopeptidase-P. Biochem. Biophys. Res. Commun. 32 (1968) 658-663. [PMID: 4878817]
2. Yaron, A. and Berger, A. Aminopeptidase-P. Methods Enzymol. 19 (1970) 522-534
3. Fleminger, G., Carmel, A. and Yaron, A. Fluorogenic substrates for bacterial aminopeptidase P and its analogs detected in human serum and calf lung. Eur. J. Biochem. 125 (1982) 609-615. [PMID: 6749499]
4. Orawski, A.T., Susz, J.P. and Simmons, W.H. Aminopeptidase-P from bovine lung - solubilization, properties, potential role in bradykinin degradation. Mol. Cell. Biochem. 75 (1987) 123-132. [PMID: 3627107]
5. Hooper, N.M., Hryszko, J. and Turner, A.J. Purification and characterization of pig kidney aminopeptidase P. Biochem. J. 267 (1990) 509-515. [PMID: 2139778]
Accepted name: bacterial leucyl aminopeptidase
Reaction: Release of an N-terminal amino acid, preferentially leucine, but not glutamic or aspartic acids
Other names: Aeromonas proteolytica aminopeptidase
Comments: A zinc enzyme. Forms of the enzyme have been isolated from Aeromonas proteolytica, Escherichia coli and Streptococcus thermophilus. Examples are known from peptidase families M17 and M28 (of leucyl aminopeptidase and aminopeptidase Y, respectively)
Links to other databases: BRENDA, EXPASY, KEGG, MEROPS, Metacyc, PDB, CAS registry number: 37288-67-8
References
1. Prescott, J.M. and Wilkes, S.H. Aeromonas aminopeptidase: purification and some general properties. Arch. Biochem. Biophys. 117 (1966) 328-336. [PMID: 4961737]
2. Dick, A.J., Matheson, A.T. and Wang, J.H. A ribosomal-bound aminopeptidase in Escherichia coli B: purification and properties. Can. J. Biochem. 48 (1970) 1181-1188. [PMID: 4920230]
3. Rabier, D. and Desmazeaud, M.J. Inventaire des différentes activités peptidasiques intracellulaires de Streptococcus thermophilus. Purification et propriétés d'une dipeptide-hydrolase et d'une aminopeptidase. Biochimie (Paris) 55 (1973) 389-404. [PMID: 4749719]
[EC 3.4.11.11 Deleted entry: aminopeptidase (EC 3.4.11.11 created 1978, deleted 1992)]
[EC 3.4.11.12 Deleted entry: thermophilic aminopeptidase (EC 3.4.11.12 created 1978, deleted 1997)]
Accepted name: clostridial aminopeptidase
Reaction: Release of any N-terminal amino acid, including proline and hydroxyproline, but no cleavage of Xaa-Pro-
Other names: Clostridium histolyticum aminopeptidase
Comments: A secreted enzyme from Clostridium histolyticum, requiring Mn2+ or Co2+
Links to other databases: BRENDA, EXPASY, KEGG, MEROPS, Metacyc, CAS registry number: 59680-69-2
References
1. Kessler, E. and Yaron, A. A novel aminopeptidase from Clostridium histolyticum. Biochem. Biophys. Res. Commun. 50 (1973) 405-412. [PMID: 4631895]
2. Kessler, E. and Yaron, A. An extracellular aminopeptidase from Clostridium histolyticum. Eur. J. Biochem. 63 (1976) 271-287. [PMID: 4318]
3. Kessler, E. and Yaron, A. Extracellular aminopeptidase from Clostridium histolyticum. Methods Enzymol. 45 (1976) 544-552. [PMID: 13266]
Accepted name: cytosol alanyl aminopeptidase
Reaction: Release of an N-terminal amino acid, preferentially alanine, from a wide range of peptides, amides and arylamides
Other names: arylamidase; aminopolypeptidase; thiol-activated aminopeptidase; human liver aminopeptidase; puromycin-sensitive aminopeptidase; soluble alanyl aminopeptidase; cytosol aminopeptidase III; alanine aminopeptidase
Comments: A puromycin-sensitive, Co2+-activated zinc-sialoglycoprotein that is generally cytosolic. Multiple forms are widely distributed in mammalian tissues and body fluids. In peptidase family M1 (membrane alanyl aminopeptidase family)
Links to other databases: BRENDA, EXPASY, KEGG, MEROPS, Metacyc, PDB, CAS registry number: 243859-94-1
References
1. Starnes, W.L. and Behal, F.J. A human liver aminopeptidase. The amino acid and carbohydrate content, and some physical properties of a sialic acid containing glycoprotein. Biochemistry 13 (1974) 3221-3227. [PMID: 4841062]
2. Kao, Y.J., Starnes, W.L. and Behal, F.J. Human kidney alanine aminopeptidase: physical and kinetic properties of a sialic acid containing glycoprotein. Biochemistry 17 (1978) 2990-2994. [PMID: 698181]
3. Sidorowicz, W., Hsia, W.-C., Maslej-Zownir, M. and Behal, F.J. Multiple molecular forms of human alanine aminopeptidase: imunochemical properties. Clin. Chim. Acta 107 (1980) 245-256. [PMID: 6108169]
Accepted name: aminopeptidase Y
Reaction: Preferentially, release of N-terminal lysine
Other names: aminopeptidase Co; aminopeptidase (cobalt-activated); lysyl aminopeptidase
Comments: Requires Co2+; inhibited by Zn2+ and Mn2+. An enzyme best known from Saccharomyces cerevisiae that hydrolyses Lys-NHPhNO2 and, more slowly, Arg-NHPhNO2. Type example of peptidase family M28
Links to other databases: BRENDA, EXPASY, KEGG, MEROPS, Metacyc, CAS registry number: 114796-97-3
References
1. Achstetter, T., Ehmann, C. and Wolf, D.H. Aminopeptidase Co, a new yeast peptidase. Biochem. Biophys. Res. Commun. 109 (1982) 341-347. [PMID: 6758786]
2. Yasuhara, T., Nakai, T. and Ohashi, A. Aminopeptidase Y, a new aminopeptidase from Saccharomyces cerevisiae. Purification, properties, localization, and processing by protease B. J. Biol. Chem. 269 (1994) 13644-13650. [PMID: 8175799]
3. Nishizawa, M., Yasuhara, T., Nakai, T., Fujiki, Y. and Ohashi, A. Molecular cloning of the aminopeptidase Y gene of Saccharomyces cerevisiae. Sequence analysis and gene disruption of a new aminopeptidase. J. Biol. Chem. 269 (1994) 13651-13655. [PMID: 8175800]
Accepted name: Xaa-Trp aminopeptidase
Reaction: Release of a variety of N-terminal residues (especially glutamate and leucine) from peptides, provided tryptophan (or at least phenylalanine or tyrosine) is the penultimate residue. Also acts on GluTrp, LeuTrp and a number of other dipeptides
Other names: aminopeptidase W; aminopeptidase X-Trp; X-Trp aminopeptidase
Comments: A glycoprotein containing Zn2+, from renal and intestinal brush border membranes
Links to other databases: BRENDA, EXPASY, KEGG, MEROPS, Metacyc, CAS registry number: 137010-33-4
References
1. Gee, N.S. and Kenny, A.J. Proteins of the kidney microvillar membrane. The 130kDa protein in pig kidney, recognised by monoclonal antibody GK5C1, is an ectoenzyme with aminopeptidase activity. Biochem. J. 230 (1985) 753-764. [PMID: 4062876]
2. Gee, N.S. and Kenny, A.J. Proteins of the kidney microvillar membrane. Enzymic and molecular properties of aminopeptidase W. Biochem. J. 246 (1987) 97-102. [PMID: 2890346]
Accepted name: tryptophanyl aminopeptidase
Reaction: Preferential release of N-terminal tryptophan
Other names: tryptophan aminopeptidase; L-tryptophan aminopeptidase
Comments: From Trichosporon cutaneum. Also acts on L-tryptophanamide. Requires Mn2+
Links to other databases: BRENDA, EXPASY, KEGG, MEROPS, Metacyc, CAS registry number: 76689-19-5
References
1. Iwayama, A., Kimura, T., Adachi, O. and Ameyama, M. Crystallization and characterization of a novel aminopeptidase from Trichosporon cutaneum. Agric. Biol. Chem. 47 (1983) 2483-2493
Accepted name: methionyl aminopeptidase
Reaction: Release of N-terminal amino acids, preferentially methionine, from peptides and arylamides
Other names: methionine aminopeptidase; peptidase M; L-methionine aminopeptidase; MAP
Comments: Membrane-bound enzyme present in both prokaryotes and eukaryotes. Type example of peptidase family M24. Releases methionine from nascent peptides
Links to other databases: BRENDA, EXPASY, KEGG, MEROPS, Metacyc, PDB, CAS registry number: 61229-81-0
References
1. Yoshida, A. and Lin, M. NH2-terminal formylmethionine- and NH2-terminal methionine-cleaving enzymes in rabbits. J. Biol. Chem. 247 (1972) 952-957. [PMID: 4110013]
2. Tsunasawa, S., Stewart, J.W. and Sherman, F. Acylamino acid-releasing enzyme from rat liver. J. Biol. Chem. 260 (1985) 5832-5391. [PMID: 2985590]
3. Freitas, J.O., Jr, Termignoni, C. and Guimaraes, J.A. Methionine aminopeptidase associated with liver mitochondria and microsomes. Int. J. Biochem. 17 (1985) 1285-1291. [PMID: 3937747]
4. Ben-Bassat, A., Bauer, K., Chang, S.-Y., Myambo, K., Boosman, A. and Chang, S. Processing of the initiation methionine from proteins: properties of Escherichia coli methionine aminopeptidase and its gene structure. J. Bacteriol. 169 (1987) 751-757. [PMID: 3027045]
5. Roderick, S.L. and Mathews, B.W. Crystallization of methionine aminopeptidase from Escherichia coli. J. Biol. Chem. 263 (1988) 16531 only. [PMID: 3141408]
Accepted name: D-stereospecific aminopeptidase
Reaction: Release of an N-terminal D-amino acid from a peptide, XaaYaa-, in which Xaa is preferably D-Ala, D-Ser or D-Thr. D-Amino acid amides and methyl esters also are hydrolysed, as is glycine amide
Other name(s): D-aminopeptidase
Comments: Known from the bacterium Ochrobactrum anthropi. In peptidase family S12 (D-Ala-D-Ala carboxypeptidase family) [2]
Links to other databases: BRENDA, EXPASY, KEGG, MEROPS, Metacyc, PDB, CAS registry number: 57534-78-8
References
1. Asano, Y., Nakazawa, A., Kato, Y. and Kondo, K. Properties of a novel D-stereospecific aminopeptidase from Ochrobactrum anthropi. J. Biol. Chem. 264 (1989) 14233-14239. [PMID: 2760064]
2. Asano, Y., Kato, Y., Yamada, A. and Kondo, K. Structural similarity of D-aminopeptidase to carboxypeptidase DD and β-lactamases. Biochemistry 31 (1992) 2316-2328. [PMID: 1540587]
Accepted name: aminopeptidase Ey
Reaction: Differs from other aminopeptidases in broad specificity for amino acids in the P1 position and the ability to hydrolyse peptides of four or five residues that contain Pro in the P1' position
Comments: A zinc glycoprotein In peptidase family M1 (membrane alanyl aminopeptidase family), composed of two 150 kDa subunits. From the plasma fraction of hen egg yolk
Links to other databases: BRENDA, EXPASY, KEGG, MEROPS, Metacyc, CAS registry number: 9031-94-1
References
1. Ichishima, E., Yamagata, Y., Chiba, H., Sawaguchi, K. and Tanaka, T. Soluble and bound forms of aminopeptidase in hens egg-yolk. Agric. Biol. Chem. 53 (1989) 1867-1872.
2. Tanaka, T. and Ichishima, E. Substrate specificity of aminopeptidase Ey from hen's egg yolk. Comp. Biochem. Physiol. [B] 105 (1993) 105-110. [PMID: 7684960]
3. Tanaka, T. and Ichishima, E. Molecular properties of aminopeptidase Ey as a zinc-metalloenzyme. Int. J. Biochem. 25 (1993) 1681-1688. [PMID: 8288037]
Accepted name: aspartyl aminopeptidase
Reaction: Release of an N-terminal aspartate or glutamate from a peptide, with a preference for aspartate
Comments: Aminoacyl-arylamides are poor substrates. This is an abundant cytosolic enzyme in mammalian cells, In peptidase family M18 of aminopeptidase I
Links to other databases: BRENDA, EXPASY, KEGG, MEROPS, Metacyc, PDB, CAS registry number: 9074-83-3
References
1. Kelly, J.A., Neidle, E.L. and Neidle, A. An aminopeptidase from mouse brain cytosol that cleaves N-terminal acidic amino acid residues. J. Neurochem. 40 (1983) 1727-1734. [PMID: 6854330]
2. Wilk, S., Wilk, E. and Magnusson, R.P. Purification, characterization and cloning of a cytosolic aspartyl aminopeptidase. J. Biol. Chem. 273 (1998) 15961-15970. [PMID: 9632644]
Accepted name: aminopeptidase I
Reaction: Release of an N-terminal amino acid, preferably a neutral or hydrophobic one, from a polypeptide. Aminoacyl-arylamides are poor substrates
Other names: aminopeptidase III; aminopeptidase yscI; leucine aminopeptidase IV; yeast aminopeptidase I
Comments: A 640-kDa, dodecameric enzyme best known as the major vacuolar aminopeptidase of yeast, Saccharomyces cervisiae, in which species it was first given the name aminopeptidase I (one), amongst others. Activity is stimulated by both Zn2+ and Cl- ions. Type example of peptidase family M18
Links to other databases: BRENDA, EXPASY, KEGG, MEROPS, Metacyc, CAS registry number: 9031-94-1
References
1. Johnson, M.J. Isolation and properties of a pure yeast polypeptidase. J. Biol. Chem. 137 (1941) 575-586
2. Metz, G. and Rohm, K.-H. Yeast aminopeptidase I. Chemical composition and catalytic properties. Biochim. Biophys. Acta 429 (1976) 933-949. [PMID: 5147]
3. Chang, Y-H. and Smith, J.A. Molecular cloning and sequencing of genomic DNA encoding aminopeptidase I from Saccharomyces cerevisiae. J. Biol. Chem. 264 (1989) 6979-6983. [PMID: 2651436]
4. Oda, M.N., Scott, S.V., Hefner-Gravink, A., Caffarelli, A.D. and Klionsky, D.J. Identification of a cytoplasm to vacuole targeting determinant in aminopeptidase I. J. Cell Biol. 132 (1996) 999-1010. [PMID: 8601598]
Accepted name: PepB aminopeptidase
Reaction: Release of an N-terminal amino acid, Xaa, from a peptide or arylamide. Xaa is preferably Glu or Asp but may be other amino acids, including Leu, Met, His, Cys and Gln
Other name(s): Salmonella enterica serovar Typhimurium peptidase B
Comments: A 270-kDa protein composed of six 46.3-kDa subunits. The pH optimum is in the alkaline range and activity is stimulated by KCl. In peptidase family M17.
Links to other databases: BRENDA, EXPASY, KEGG, MEROPS, Metacyc, PDB, CAS registry number: 928346-44-5
References:
1. Mathew, Z., Knox, T.M. and Miller, C.G. Salmonella enterica serovar Typhimurium peptidase B is a leucyl aminopeptidase with specificity for acidic amino acids. J. Bacteriol. 182 (2000) 3383-3393. [PMID: 10852868]
Accepted name: aminopeptidase S
Reaction: Release of an N-terminal amino acid with a preference for large hydrophobic amino-terminus residues
Other name(s): Mername-AA022 peptidase; SGAP; aminopeptidase (Streptomyces griseus); Streptomyces griseus aminopeptidase; S. griseus AP; double-zinc aminopeptidase
Comments: Aminopeptidases are associated with many biological functions, including protein maturation, protein degradation, cell-cycle control and hormone-level regulation [3,4]. This enzyme contains two zinc molecules in its active site and is activated by Ca2+ [4]. In the presence of Ca2+, the best substrates are Leu-Phe, Leu-Ser, Leu-pNA (aminoacyl-p-nitroanilide), Phe-Phe-Phe and Phe-Phe [3]. Peptides with proline in the P1' position are not substrates [3]. Belongs in peptidase family M28.
Links to other databases: BRENDA, EXPASY, KEGG, MEROPS, Metacyc, PDB, CAS registry number:
References:
1. Spungin, A. and Blumberg, S. Streptomyces griseus aminopeptidase is a calcium-activated zinc metalloprotein. Purification and properties of the enzyme. Eur. J. Biochem. 183 (1989) 471-477. [PMID: 2503378]
2. Ben-Meir, D., Spungin, A., Ashkenazi, R. and Blumberg, S. Specificity of Streptomyces griseus aminopeptidase and modulation of activity by divalent metal ion binding and substitution. Eur. J. Biochem. 212 (1993) 107-112. [PMID: 8444149]
3. Arima, J., Uesugi, Y., Iwabuchi, M. and Hatanaka, T. Study on peptide hydrolysis by aminopeptidases from Streptomyces griseus, Streptomyces septatus and Aeromonas proteolytica. Appl. Microbiol. Biotechnol. 70 (2006) 541-547. [PMID: 16080009]
4. Fundoiano-Hershcovitz, Y., Rabinovitch, L., Langut, Y., Reiland, V., Shoham, G. and Shoham, Y. Identification of the catalytic residues in the double-zinc aminopeptidase from Streptomyces griseus. FEBS Lett. 571 (2004) 192-196. [PMID: 15280041]
5. Gilboa, R., Greenblatt, H.M., Perach, M., Spungin-Bialik, A., Lessel, U., Wohlfahrt, G., Schomburg, D., Blumberg, S. and Shoham, G. Interactions of Streptomyces griseus aminopeptidase with a methionine product analogue: a structural study at 1.53 Å resolution. Acta Crystallogr. D Biol. Crystallogr. 56 (2000) 551-558. [PMID: 10771423]
Accepted name: β-peptidyl aminopeptidase
Reaction: Cleaves N-terminal β-homoamino acids from peptides composed of 2 to 6 amino acids
Other name(s): BapA (ambiguous)
Comments: Sphingosinicella xenopeptidilytica strain 3-2W4 is able to utilize the β-peptides β-homoVal-β-homoAla-β-homoLeu and β-homoAla-β-homoLeu as sole carbon and energy sources [2].
Links to other databases: BRENDA, EXPASY, KEGG, MEROPS, Metacyc, CAS registry number:
References:
1. Heck, T., Limbach, M., Geueke, B., Zacharias, M., Gardiner, J., Kohler, H.P. and Seebach, D. Enzymatic degradation of β- and mixed α,β-oligopeptides. Chem. Biodivers. 3 (2006) 1325-1348. [PMID: 17193247]
2. Geueke, B., Namoto, K., Seebach, D. and Kohler, H.P. A novel β-peptidyl aminopeptidase (BapA) from strain 3-2W4 cleaves peptide bonds of synthetic β-tri- and β-dipeptides. J. Bacteriol. 187 (2005) 5910-5917. [PMID: 16109932]
3. Geueke, B., Heck, T., Limbach, M., Nesatyy, V., Seebach, D. and Kohler, H.P. Bacterial β-peptidyl aminopeptidases with unique substrate specificities for β-oligopeptides and mixed β,α-oligopeptides. FEBS J. 273 (2006) 5261-5272. [PMID: 17064315]
4. Heck, T., Kohler, H.P., Limbach, M., Flögel, O., Seebach, D. and Geueke, B. Enzyme-catalyzed formation of β-peptides: β-peptidyl aminopeptidases BapA and DmpA acting as β-peptide-synthesizing enzymes. Chem. Biodivers. 4 (2007) 2016. [PMID: 17886858]
Accepted name: intermediate cleaving peptidase 55
Reaction: The enzyme cleaves the Pro36-Pro37 bond of cysteine desulfurase (EC 2.8.1.7) removing three amino acid residues (Tyr-Ser-Pro) from the N-terminus after cleavage by mitochondrial processing peptidase.
Other name(s): Icp55; mitochondrial intermediate cleaving peptidase 55 kDa
Comments: Icp55 removes the destabilizing N-terminal amino acid residues that are left after cleavage by the mitochondrial processing peptidase, leading to the stabilisation of the substrate. The enzyme can remove single amino acids or a short peptide, as in the case of cysteine desulfurase (EC 2.8.1.7), where three amino acids are removed.
Links to other databases: BRENDA, EXPASY, KEGG, MEROPS, Metacyc, PDB, CAS registry number:
References:
1. Naamati, A., Regev-Rudzki, N., Galperin, S., Lill, R. and Pines, O. Dual targeting of Nfs1 and discovery of its novel processing enzyme, Icp55. J. Biol. Chem. 284 (2009) 30200-30208. [PMID: 19720832]
2. Vogtle, F.N., Wortelkamp, S., Zahedi, R.P., Becker, D., Leidhold, C., Gevaert, K., Kellermann, J., Voos, W., Sickmann, A., Pfanner, N. and Meisinger, C. Global analysis of the mitochondrial N-proteome identifies a processing peptidase critical for protein stability. Cell 139 (2009) 428-439. [PMID: 19837041]
Accepted name: archaeal arginyl aminopeptidase
Reaction: Release of an N-terminal L-arginine from a protein with only minimal activity against other amino acids. L-Arg-7-amido-4-methylcoumarin is the best artificial substrate.
Other name(s): arginyl aminopeptidase PH1704; PH1704; PfpI peptidase; C56.001 (Merops Identifier)
Comments: The enzyme from the archaeon Pyrococcus horikoshii OT3 is thermostable. In that enzyme Cys100 is the nucleophile responsible for the proteolytic activity, while Tyr120 regulates the catalytic conformation of Cys100 through a hydrogen bond, thereby affecting enzyme activity. The activity with L-Arginine is 90-300 times higher than with other N-terminal amino acids. The enzyme shows low endopeptidase activity.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:
References:
1. Du, X., Choi, I.G., Kim, R., Wang, W., Jancarik, J., Yokota, H. and Kim, S.H. Crystal structure of an intracellular protease from Pyrococcus horikoshii at 2-Å resolution. Proc. Natl. Acad. Sci. USA 97 (2000) 14079-14084. [PMID: 11114201]
2. Zhan, D., Han, W. and Feng, Y. Experimental and computational studies indicate the mutation of Glu12 to increase the thermostability of oligomeric protease from Pyrococcus horikoshii. J Mol Model 17 (2011) 1241-1249. [PMID: 20711794]
3. Zhan, D., Bai, A., Yu, L., Han, W. and Feng, Y. Characterization of the PH1704 protease from Pyrococcus horikoshii OT3 and the critical functions of Tyr120. PLoS One 9 (2014) e103902. [PMID: 25192005]
Contents
EC 3.4.13.1 now EC 3.4.13.18
EC 3.4.13.2 now EC 3.4.13.18
EC 3.4.13.3 deleted, covered by EC 3.4.13.18 and EC 3.4.13.20
EC 3.4.13.4 Xaa-Arg dipeptidase
EC 3.4.13.5 Xaa-Methyl-His dipeptidase
EC 3.4.13.6 now EC 3.4.11.2
EC 3.4.13.7 Glu-Glu dipeptidase
EC 3.4.13.8 now EC 3.4.17.21
EC 3.4.13.9 Xaa-Pro dipeptidase
EC 3.4.13.10 now EC 3.4.19.5
EC 3.4.13.11 deleted, included in EC 3.4.13.18
EC 3.4.13.12 Met-Xaa dipeptidase
EC 3.4.13.13 deleted, included in EC 3.4.13.3
EC 3.4.13.14 deleted
EC 3.4.13.15 deleted, included in EC 3.4.13.18
EC 3.4.13.16 deleted
EC 3.4.13.17 non-stereospecific dipeptidase
EC 3.4.13.18 cytosol nonspecific dipeptidase
EC 3.4.13.19 membrane dipeptidase
EC 3.4.13.20 β-Ala-His dipeptidase
EC 3.4.13.21 dipeptidase E
EC 3.4.13.22 D-Ala-D-Ala dipeptidase
EC 3.4.13.23 cysteinylglycine-S-conjugate dipeptidase
[EC 3.4.13.1 Transferred entry: now EC 3.4.13.18 - cytosol nonspecific dipeptidase (EC 3.4.13.1 created 1972, deleted 1978 [transferred to EC 3.4.13.11, deleted 1992])]
[EC 3.4.13.2 Transferred entry: now EC 3.4.13.18 - cytosol nonspecific dipeptidase (EC 3.4.13.2 created 1972, deleted 1978 [transferred to EC 3.4.13.11, deleted 1992])]
[EC 3.4.13.3 Deleted entry: Xaa-His dipeptidase. The activity is covered by EC 3.4.13.18, cytosol nonspecific dipeptidase and EC 3.4.13.20, β-Ala-His dipeptidase. (EC 3.4.13.3 created 1961 as EC 3.4.3.3, transferred 1972 to EC 3.4.13.3, modified 1989 (EC 3.4.13.13 created 1981, incorporated 1992), deleted 2011)]
Accepted name: Xaa-Arg dipeptidase
Reaction: Preferential hydrolysis of XaaArg, XaaLys or Xaaornithine dipeptides
Other names: aminoacyl-lysine dipeptidase; N2-(4-amino-butyryl)-L-lysine hydrolase; X-Arg dipeptidase
Comments: Widely distributed in mammals
Links to other databases: BRENDA, EXPASY, KEGG, MEROPS, Metacyc, PDB, CAS registry number: 37288-72-5
References
1. Kumon, A., Matsuoka, Y., Kakimoto, Y., Nakajima, T. and Sano, I. A peptidase that hydrolyzes α-N-(γ-aminobutyryl)lysine. Biochim. Biophys. Acta 200 (1970) 466-474. [PMID: 5436646]
Accepted name: Xaa-methyl-His dipeptidase
Reaction: Hydrolysis of anserine (β-alanylNπ-methyl-L-histidine), carnosine, homocarnosine, glycylleucine and other dipeptides with broad specificity
Other names: anserinase; aminoacyl-methylhistidine dipeptidase; acetylhistidine deacetylase; N-acetylhistidine deacetylase; α-N-acetyl-L-histidine aminohydrolase; X-methyl-His dipeptidase
Links to other databases: BRENDA, EXPASY, KEGG, MEROPS, Metacyc, CAS registry number: 9027-38-7
References
1. Jones, N.R. The free amino acids of fish. 1-Methylhistidine and β-alanine liberation by skeletal muscle anserinase of codling (Gadus callarias). Biochem. J. 60 (1955) 81-87
2. Baslow, M.H. and Lenney, J.F. α-N-Acetyl-L-histidine amidohydrolase activity from the brain of the skipjack tuna Katsuwonus pelamis. Can. J. Biochem. 45 (1967) 337-340. [PMID: 6067033]
3. Lenney, J.F., Baslow, M.H. and Sugiyama, G.H. Similarity of tuna N-acetylhistidine deacetylase and cod fish anserinase. Comp. Biochem. Physiol. B Comp. Biochem. 61 (1978) 253-258. [PMID: 318374]
[EC 3.4.13.6 Transferred entry: now EC 3.4.11.2 - Membrane alanyl aminopeptidase (EC 3.4.13.6 created 1961 as EC 3.4.3.5, transferred 1972 to EC 3.4.13.6)]
Accepted name: Glu-Glu dipeptidase
Reaction: Hydrolysis of the GluGlu dipeptide
Other names: α-glutamyl-glutamate dipeptidase; glutamylglutamic arylamidase
Comments: It is unclear whether the specificity of this enzyme extends to other α-glutamyl dipeptides
Links to other databases: BRENDA, EXPASY, KEGG, MEROPS, Metacyc, CAS registry number: 37288-73-6
References
1. Pratt, A.G., Crawford, E.J. and Friedkin, M. The hydrolysis of mono-, di-, and triglutamate derivatives of folic acid with bacterial enzymes. J. Biol. Chem. 243 (1968) 6367-6372. [PMID: 5726892]
[EC 3.4.13.8 Transferred entry: now EC 3.4.13.18 - cytosol nonspecific dipeptidase (EC 3.4.13.8 created 1961 as EC 3.4.3.6, transferred 1972 to EC 3.4.13.8)]
Accepted name: Xaa-Pro dipeptidase
Reaction: Hydrolysis of XaaPro dipeptides; also acts on aminoacyl-hydroxyproline analogs. No action on Pro-Pro
Other names: prolidase; imidodipeptidase; proline dipeptidase; peptidase D; γ-peptidase; X-Pro dipeptidase
Comments: A Mn2+-activated enzyme, In peptidase family M24 (methionyl aminopeptidase family); cytosolic from most animal tissues. Formerly EC 3.4.3.7
Links to other databases: BRENDA, EXPASY, KEGG, MEROPS, Metacyc, PDB, CAS registry number: 9025-32-5
References
1. Davis, N.C. and Smith, E.L. Purification and some properties of prolidase of swine kidney. J. Biol. Chem. 224 (1957) 261-275
2. Sjöström, H., Norén, O. and Josefsson, L. Purification and specificity of pig intestinal prolidase. Biochim. Biophys. Acta 327 (1973) 457-470. [PMID: 4778946]
3. Baksi, K. and Radhakrishnan, A.N. Purification and properties of prolidase (imidodipeptidase) from monkey small intestine. Indian J. Biochem. Biophys. 11 (1974) 7-11. [PMID: 4435812]
4. Browne, P. and O'Cuinn, G. The purification and characterization of a proline dipeptidase from guinea pig brain. J. Biol. Chem. 258 (1983) 6147-6154. [PMID: 6853481]
[EC 3.4.13.10 Transferred entry: now EC 3.4.19.5 - β-aspartyl-peptidase (EC 3.4.13.10 created 1972, deleted 1992)]
[EC 3.4.13.11 Transferred entry: now included in EC 3.4.13.18 - cytosol nonspecific dipeptidase, and EC 3.4.13.19 - membrane dipeptidase (EC 3.4.13.11 created 1972, deleted 1992)]
Accepted name: Met-Xaa dipeptidase
Reaction: Hydrolysis of MetXaa dipeptides
Other names: methionyl dipeptidase; dipeptidase M; Met-X dipeptidase
Comments: A Mn2+-activated Escherichia coli enzyme with thiol dependence
Links to other databases: BRENDA, EXPASY, KEGG, MEROPS, Metacyc, CAS registry number: 37341-91-6
References
1. Brown, J.L. Purification and properties of dipeptidase M from Escherichia coli B. J. Biol. Chem. 248 (1973) 409-416. [PMID: 4567782]
[EC 3.4.13.13 Transferred entry: now included with EC 3.4.13.3 - Xaa-His dipeptidase (EC 3.4.13.13 created 1981, deleted 1992)]
[EC 3.4.13.14 Deleted entry: γ-glutamyldipeptidase (EC 3.4.13.14 created 1989, deleted 1992)]
[EC 3.4.13.15 Transferred entry: now included with EC 3.4.13.18 - cytosol nonspecific dipeptidase (EC 3.4.13.15 created 1989, deleted 1992)]
[EC 3.4.13.16 Deleted entry: aspartylphenylalanine dipeptidase (EC 3.4.13.16 created 1989, deleted 1992)]
Accepted name: non-stereospecific dipeptidase
Reaction: Hydrolysis of dipeptides containing either D- or L-amino acids or both
Other names: peptidyl-D-amino acid hydrolase; D-(or L-)aminoacyl-dipeptidase
Comments: A digestive enzyme of cephalopods
Links to other databases: BRENDA, EXPASY, KEGG, MEROPS, Metacyc, CAS registry number: 90371-43-0
References
1. D'Aniello, A. and Strazullo, L. Peptidyl-D-amino acid hydrolase from Loligo vulgaris Lam. J. Biol. Chem. 259 (1984) 4237-4243. [PMID: 6444201]
Accepted name: cytosol nonspecific dipeptidase
Reaction: Hydrolysis of dipeptides, preferentially hydrophobic dipeptides including prolyl amino acids
Other names: N2-β-alanylarginine dipeptidase; glycyl-glycine dipeptidase; glycyl-leucine dipeptidase; iminodipeptidase; peptidase A; Pro-X dipeptidase; prolinase; prolyl dipeptidase; prolylglycine dipeptidase; iminodipeptidase; prolinase; L-prolylglycine dipeptidase; prolylglycine dipeptidase; diglycinase; Gly-Leu hydrolase; glycyl-L-leucine dipeptidase; glycyl-L-leucine hydrolase; glycyl-L-leucine peptidase; L-amino-acyl-L-amino-acid hydrolase; glycylleucine peptidase; glycylleucine hydrolase; glycylleucine dipeptide hydrolase; non-specific dipeptidase; human cytosolic non-specific dipeptidase; glycyl-L-leucine hydrolase; glycyl-glycine dipeptidase
Comments: A zinc enzyme with broad specificity, varying somewhat with source species. Activated and stabilized by dithiothreitol and Mn2+. Inhibited by bestatin and leucine. Formerly EC 3.4.3.1, EC 3.4.3.2, EC 3.4.3.6, EC 3.4.13.1, EC 3.4.13.2, EC 3.4.13.8, EC 3.4.13.11 and EC 3.4.13.15
Links to other databases: BRENDA, EXPASY, KEGG, MEROPS, Metacyc, PDB, CAS registry number: 9025-31-4
References
1. Bauer, K. Cytosol non-specific dipeptidase. In: Handbook of Proteolytic Enzymes (Barrett, A. J., Rawlings, N. D. and Woessner, J. F., eds), pp. 1520-1522 (1998) Academic Press, London
Accepted name: membrane dipeptidase
Reaction: Hydrolysis of dipeptides
Other name(s): renal dipeptidase; dehydropeptidase I (DPH I); dipeptidase (ambiguous); aminodipeptidase; dipeptide hydrolase (ambiguous); dipeptidyl hydrolase (ambiguous); nonspecific dipeptidase; glycosyl-phosphatidylinositol-anchored renal dipeptidase; MDP
Comments: A membrane-bound, zinc enzyme with broad specificity. Abundant in the kidney cortex. Inhibited by bestatin and cilastatin. Type example of peptidase family M19.
Links to other databases: BRENDA, EXPASY, KEGG, MEROPS, Metacyc, PDB, CAS registry number: 9031-99-6
References:
1. Campbell, B., Lin, H., Davis, R. and Ballew, E. The purification and properties of a particulate renal dipeptidase. Biochim. Biophys. Acta 118 (1966) 371-386. [PMID: 5961612]
2. Campbell, B.J. Renal dipeptidase. Methods Enzymol. 19 (1970) 722-729.
3. Kropp, H., Sundelof, J.G., Hajdu, R. and Kahan, F.M. Metabolism of thienamycin and related carbapenem antibiotics by renal dipeptidase, dehydropeptidase-I. Antimicrob. Agents Chemother. 22 (1982) 62-70. [PMID: 7125632]
4. Hooper, N.M., Keen, J.N. and Turner, A.J. Characterization of the glycosyl-phosphatidylinositol-anchored human renal dipeptidase reveals that it is more extensively glycosylated than the pig enzyme. Biochem. J. 265 (1990) 429-433. [PMID: 2137335]
Accepted name: β-Ala-His dipeptidase
Reaction: Preferential hydrolysis of the β-AlaHis dipeptide (carnosine), and also anserine, XaaHis dipeptides and other dipeptides including homocarnosine
Other names: serum carnosinase
Comments: Present in the serum of humans and higher primates, but not in the serum of other mammals. Activated by Cd2+ and citrate. Belongs In peptidase family M20.
Links to other databases: BRENDA, EXPASY, KEGG, MEROPS, Metacyc, PDB, CAS registry number: 525589-43-9
References
1. Lenney, J.F., George, R.P., Weiss, A.M., Kucera, C.M., Chan, P.W.H. and Rinzler, G.S. Human serum carnosinase: characterization, distinction from cellular carnosinase, and activation by cadmium. Clin. Chim. Acta 123 (1982) 221-231. [PMID: 7116644]
2. Jackson, M.C., Kucera, C.M. and Lenney, J.F. Purification and properties of human serum carnosinase. Clin. Chim. Acta 196 (1991) 193-206. [PMID: 1903095]
Accepted name: dipeptidase E
Reaction: Dipeptidase E catalyses the hydrolysis of dipeptides AspXaa. It does not act on peptides with N-terminal Glu, Asn or Gln, nor does it cleave isoaspartyl peptides
Other names: aspartyl dipeptidase; peptidase E; PepE gene product (Salmonella typhimurium)
Comments: A free carboxy group is not absolutely required in the substrate since Asp-Phe-NH2 and Asp-Phe-OMe are hydrolysed somewhat more slowly than dipeptides with free C-termini. No peptide larger than a C-blocked dipeptide is known to be a substrate. Asp-NH-Np is hydrolysed and is a convenient substrate for routine assay. The enzyme is most active near pH 7.0, and is not inhibited by di-isopropylfluorophosphate or phenylmethanesulfonyl fluoride. Belongs In peptidase family S51.
Links to other databases: BRENDA, EXPASY, KEGG, MEROPS, Metacyc, PDB, CAS registry number:
References
1. Håkansson, K., Wang, A.H.J. and Miller, C.G. The structure of aspartyl dipeptidase reveals a unique fold with a Ser-His-Glu catalytic triad. Proc. Natl. Acad. Sci. USA 97 (2000) 14097-14102. [PMID: 11106384]
2. Lassy, R.A.L. and Miller, C.G. Peptidase E, a peptidase specific for N-terminal aspartic dipeptides, is a serine hydrolase. J. Bacteriol. 182 (2000) 2536-2543. [PMID: 10762256]
Accepted name: D-Ala-D-Ala dipeptidase
Reaction: D-Ala-D-Ala + H2O = 2 D-Ala
Other name(s): D-alanyl-D-alanine dipeptidase; vanX D-Ala-D-Ala dipeptidase; VanX
Comments: A Zn2+-dependent enzyme [4]. The enzyme protects Enterococcus faecium from the antibiotic vancomycin, which can bind to the -D-Ala-D-Ala sequence at the C-terminus of the peptidoglycan pentapeptide (see diagram). This enzyme reduces the availability of the free dipeptide D-Ala-D-Ala, which is the precursor for this pentapeptide sequence, allowing D-Ala-(R)-lactate (for which vancomycin has much less affinity) to be added to the cell wall instead [2,3]. The enzyme is stereospecific, as L-Ala-L-Ala, D-Ala-L-Ala and L-Ala-D-Ala are not substrates [2]. Belongs in peptidase family M15.
Links to other databases: BRENDA, EXPASY, KEGG, MEROPS, Metacyc, CAS registry number:
References:
1. Reynolds, P.E., Depardieu, F., Dutka-Malen, S., Arthur, M. and Courvalin, P. Glycopeptide resistance mediated by enterococcal transposon Tn1546 requires production of VanX for hydrolysis of D-alanyl-D-alanine. Mol. Microbiol. 13 (1994) 1065-1070. [PMID: 7854121]
2. Wu, Z., Wright, G.D. and Walsh, C.T. Overexpression, purification, and characterization of VanX, a D-, D-dipeptidase which is essential for vancomycin resistance in Enterococcus faecium BM4147. Biochemistry 34 (1995) 2455-2463. [PMID: 7873524]
3. McCafferty, D.G., Lessard, I.A. and Walsh, C.T. Mutational analysis of potential zinc-binding residues in the active site of the enterococcal D-Ala-D-Ala dipeptidase VanX. Biochemistry 36 (1997) 10498-10505. [PMID: 9265630]
4. Bussiere, D.E., Pratt, S.D., Katz, L., Severin, J.M., Holzman, T. and Park, C.H. The structure of VanX reveals a novel amino-dipeptidase involved in mediating transposon-based vancomycin resistance. Mol. Cell. 2 (1998) 75-84. [PMID: 9702193]
5. Tan, A.L., Loke, P. and Sim, T.S. Molecular cloning and functional characterisation of VanX, a D-alanyl-D-alanine dipeptidase from Streptomyces coelicolor A3(2). Res. Microbiol. 153 (2002) 27-32. [PMID: 11881895]
6. Matthews, M.L., Periyannan, G., Hajdin, C., Sidgel, T.K., Bennett, B. and Crowder, M.W. Probing the reaction mechanism of the D-ala-D-ala dipeptidase, VanX, by using stopped-flow kinetic and rapid-freeze quench EPR studies on the Co(II)-substituted enzyme. J. Am. Chem. Soc. 128 (2006) 13050-13051. [PMID: 17017774]
Accepted name: cysteinylglycine-S-conjugate dipeptidase
Reaction: an [L-cysteinylglycine]-S-conjugate + H2O = an L-cysteine-S-conjugate + glycine
Other name(s): tpdA (gene name); LAP3 (gene name)
Systematic name: cysteinylglycine-S-conjugate dipeptide hydrolase
Comments: The enzyme participates in a widespread glutathione-mediated detoxification pathway. In animals the activity is usually catalysed by enzymes that have numerous additional activities, such as EC 3.4.11.1 , leucyl aminopeptidase, EC 3.4.11.2, membrane alanyl aminopeptidase, and EC 3.4.13.19, membrane dipeptidase. However, in the bacterium Corynebacterium sp. Ax20, which degrades axillary secretions, the enzyme appears to be specific for this task.
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, PDB, CAS registry number:
References:
1. SEMENZA G Chromatographic purification of cysteinyl-glycinase. Biochim. Biophys. Acta 24 (1957) 401-413. [PMID: 13436444]
2. Rankin, B.B., McIntyre, T.M. and Curthoys, N.P. Brush border membrane hydrolysis of S-benzyl-cysteine-p-nitroanilide, and activity of aminopeptidase M. Biochem. Biophys. Res. Commun. 96 (1980) 991-996. [PMID: 6108111]
3. Hirota, T., Nishikawa, Y., Takahagi, H., Igarashi, T. and Kitagawa, H. Simultaneous purification and properties of dehydropeptidase-I and aminopeptidase-M from rat kidney. Res Commun Chem Pathol Pharmacol 49 (1985) 435-445. [PMID: 2865778]
4. Josch, C., Klotz, L.O. and Sies, H. Identification of cytosolic leucyl aminopeptidase (EC 3.4.11.1) as the major cysteinylglycine-hydrolysing activity in rat liver. Biol. Chem. 384 (2003) 213-218. [PMID: 12675513]
5. Emter, R. and Natsch, A. The sequential action of a dipeptidase and a β-lyase is required for the release of the human body odorant 3-methyl-3-sulfanylhexan-1-ol from a secreted Cys-Gly-(S) conjugate by Corynebacteria. J. Biol. Chem 283 (2008) 20645-20652. [PMID: 18515361]
EC 3.4.14.1 dipeptidyl-peptidase I
EC 3.4.14.2 dipeptidyl-peptidase II
EC 3.4.14.3 now EC 3.4.19.1
EC 3.4.14.4 dipeptidyl-peptidase III
EC 3.4.14.5 dipeptidyl-peptidase IV
EC 3.4.14.6 dipeptidyl-dipeptidase
EC 3.4.14.7 deleted
EC 3.4.14.8 now EC 3.4.14.9
EC 3.4.14.9 tripeptidyl-peptidase I
EC 3.4.14.10 tripeptidyl-peptidase II
EC 3.4.14.11 Xaa-Pro dipeptidyl-peptidase
EC 3.4.14.12 prolyltripeptidyl aminopeptidase
EC 3.4.14.13 γ-D-glutamyl-L-lysine dipeptidyl-peptidase
EC 3.4.14.14 [mycofactocin precursor peptide] peptidase
Accepted name: dipeptidyl-peptidase I
Reaction: Release of an N-terminal dipeptide, Xaa-YaaZaa-, except when Xaa is Arg or Lys, or Yaa or Zaa is Pro
Other names: cathepsin C; dipeptidyl aminopeptidase I; dipeptidyl transferase; cathepsin C; dipeptidyl transferase; dipeptide arylamidase I; DAP I
Comments: A Cl--dependent, lysosomal cysteine-type peptidase maximally active at acidic pH. Also polymerizes dipeptide amides, arylamides and esters at neutral pH. In peptidase family C1 (papain family). Formerly EC 3.4.4.9
Links to other databases: BRENDA, EXPASY, KEGG, GTD, MEROPS, Metacyc, PDB, CAS registry number: 9032-68-2
References
1. Planta, R.J., Gorter, J. and Gruber, M. The catalytic properties of cathepsin C. Biochim. Biophys. Acta 89 (1964) 511-519
2. Metrione, R.M., Neves, A.G. and Fruton, J.S. Purification and properties of dipeptidyl transferase (cathepsin C). Biochemistry 5 (1966) 1597-1604. [PMID: 5961281]
3. McDonald, J.K., Zeitman, B.B., Reilly, T.J. and Ellis, S. New observations on the substrate specificity of cathepsin C (dipeptidyl aminopeptidase I) including the degradation of β-corticotropin and other peptide hormones. J. Biol. Chem. 244 (1969) 2693-2709. [PMID: 4306035]
4. McDonald, J.K. and Schwabe, C. Intracellular exopeptidases. In Proteinases in Mammalian Cells and Tissues (Barrett, A.J. ed.), pp. 311-391 (1977) North-Holland Publishing Co, Amsterdam
Accepted name: dipeptidyl-peptidase II
Reaction: Release of an N-terminal dipeptide, Xaa-Yaa, preferentially when Yaa is Ala or Pro. Substrates are oligopeptides, preferentially tripeptides
Other names: dipeptidyl aminopeptidase II; dipeptidyl arylamidase II; carboxytripeptidase; dipeptidyl peptidase II; dipeptidyl arylamidase II; DAP II; dipeptidyl(amino)peptidase II; dipeptidylarylamidase
Comments: A lysosomal serine-type peptidase In family S28 (Pro-X carboxypeptidase family); maximally active at acidic pH
Links to other databases: BRENDA, EXPASY, KEGG, MEROPS, Metacyc, PDB, CAS registry number: 76199-23-0
References
1. McDonald, J.K., Reilly, T.J., Zeitman, B.B. and Ellis, S. Dipeptidyl arylamidase II of the pituitary. Properties of lysyl-alanyl-β-naphthylamide hydrolysis: inhibition by cations, distribution in tissues and subcellular localization. J. Biol. Chem. 243 (1968) 4143-4150. [PMID: 4969969]
2. McDonald, J.K. and Schwabe, C. Intracellular exopeptidases. In Proteinases in Mammalian Cells and Tissues (Barrett, A.J. ed.), pp. 311-391 (1977) North-Holland Publishing Co, Amsterdam
[EC 3.4.14.3 Transferred entry: now EC 3.4.19.1 - Acylaminoacyl-peptidase (EC 3.4.14.3 created 1978, deleted 1981)]
Accepted name: dipeptidyl-peptidase III
Reaction: Release of an N-terminal dipeptide from a peptide comprising four or more residues, with broad specificity. Also acts on dipeptidyl 2-naphthylamides.
Other names: dipeptidyl aminopeptidase III; dipeptidyl arylamidase III; enkephalinase B; red cell angiotensinase
Comments: A cytosolic peptidase that is active at neutral pH. It has broad activity on peptides, although it is highly selective for Arg-Arg-2-naphthylamide, at pH 9.2. Active in the hydrolysis of enkephalins. A metallopeptidase, the type example of peptidase family M49.
Links to other databases: BRENDA, EXPASY, KEGG, MEROPS, Metacyc, PDB, CAS registry number: 77464-87-0
References
1. McDonald, J.K. Dipeptidyl-peptidase III. In: Barrett, A.J., Rawlings, N.D. and Woessner, J.F. (Eds.), Handbook of Proteolytic Enzymes, Academic Press, London, 1998, pp. 536-538.
2. Fukasawa, K., Fukasawa, K.M., Iwamoto, H., Hirose, J. and Harada, M. The HELLGH motif of rat liver dipeptidyl peptidase III is involved in zinc coordination and the catalytic activity of the enzyme. Biochemistry 38 (1999) 8299-8303. [PMID: 10387075]
Accepted name: dipeptidyl-peptidase IV
Reaction: Release of an N-terminal dipeptide, Xaa-YaaZaa-, from a polypeptide, preferentially when Yaa is Pro, provided Zaa is neither Pro nor hydroxyproline
Other names: dipeptidyl aminopeptidase IV; Xaa-Pro-dipeptidyl-aminopeptidase; Gly-Pro naphthylamidase; postproline dipeptidyl aminopeptidase IV; lymphocyte antigen CD26; glycoprotein GP110; dipeptidyl peptidase IV; glycylproline aminopeptidase; glycylproline aminopeptidase; X-prolyl dipeptidyl aminopeptidase; pep X; leukocyte antigen CD26; glycylprolyl dipeptidylaminopeptidase; dipeptidyl-peptide hydrolase; glycylprolyl aminopeptidase; dipeptidyl-aminopeptidase IV; DPP IV/CD26; amino acyl-prolyl dipeptidyl aminopeptidase; T cell triggering molecule Tp103; X-PDAP
Comments: A homodimer. An integral protein of the plasma membrane of lymphocytes and other mammalian cells, In peptidase family S9 (prolyl oligopeptidase family). The reaction is similar to that of the unrelated EC 3.4.14.11 Xaa-Pro dipeptidyl-peptidase of lactococci
Links to other databases: BRENDA, EXPASY, KEGG, MEROPS, Metacyc, PDB, CAS registry number: 54249-88-6
References
1. Misumi, Y., Hayashi, Y., Arakawa, F. and Ikehara, Y. Molecular cloning and sequence analysis of human dipeptidyl peptidase IV, a serine proteinase on the cell surface. Biochim. Biophys. Acta 1131 (1992) 333-336. [PMID: 1352704]
2. David, F., Bernard, A.-M., Pierres, M. and Marguet, D. Identification of serine 624, aspartic acid 702, and histidine 734 as the catalytic triad residues of mouse dipeptidyl-peptidase IV (CD26). A member of a novel family of nonclassical serine hydrolases. J. Biol. Chem. 268 (1993) 17247-17252. [PMID: 8102366]
3. Ikehara, Y., Ogata, S. and Misumi, Y. Dipeptidyl-peptidase IV from rat liver. Methods Enzymol. 244 (1994) 215-227. [PMID: 7845210]
Accepted name: dipeptidyl-dipeptidase
Reaction: Preferential release of dipeptides from a tetrapeptide, e.g. Ala-GlyAla-Gly. Acts more slowly on Ala-AlaAla-Ala and Gly-GlyGly-Gly
Other names: dipeptidyl tetrapeptide hydrolase; dipeptidyl ligase; tetrapeptide dipeptidase
Comments: A thiol-activated peptidase from cabbage (Brassica oleracea). Tetrapeptides are formed from Ala-Ala, Gly-Gly, Ala-Gly and Gly-Ala
Links to other databases: BRENDA, EXPASY, KEGG, MEROPS, Metacyc, CAS registry number: 91608-92-3
References
1. Eng, F.W.H.T. Dipeptidyl tetrapeptide hydrolase, a new enzyme with dipeptidyl ligase activity. Can. J. Biochem. Cell. Biol. 62 (1984) 516-528
[EC 3.4.14.7 Deleted entry: tetralysine endopeptidase (EC 3.4.14.7 created 1989, deleted 1992)]
[EC 3.4.14.8 Transferred entry: now EC 3.4.14.9 - tripeptidyl-peptidase I and EC 3.4.14.10 - tripeptidyl-peptidase II (EC 3.4.14.8 created 1989, deleted 1992)]
Accepted name: tripeptidyl-peptidase I
Reaction: Release of an N-terminal tripeptide from a polypeptide, but also has endopeptidase activity.
Other name(s): tripeptidyl aminopeptidase; tripeptidyl peptidase
Comments: A lysosomal enzyme that is active at acidic pH. Deficient in classical late-infantile neuronal ceroid lipofuscinosis brain tissue. Belongs In peptidase family S53. Formerly included in EC 3.4.14.8.
Links to other databases: BRENDA, EXPASY, KEGG, MEROPS, Metacyc, PDB, CAS registry number: 151662-36-1
References:
1. Ezaki, J., Tanida, I., Kanehagi, N. and Kominami, E. A lysosomal proteinase, the late infantile neuronal ceroid lipofuscinosis gene (CLN2) product, is essential for degradation of a hydrophobic protein, the subunit c of ATP synthase. J. Neurochem. 72 (1999) 2573-2582. [PMID: 10349869]
2. Rawlings, N.D. and Barrett, A.J. Tripeptidyl-peptidase I is apparently the CLN2 protein absent in classical late-infantile neuronal ceroid lipofuscinosis. Biochim. Biophys. Acta 1429 (1999) 496-500. [PMID: 9989235]
3. Ezaki, J., Takeda-Ezaki, M., Oda, K. and Kominami, E. Characterization of endopeptidase activity of tripeptidyl peptidase-I/CLN2 protein which is deficient in classical late infantile neuronal ceroid lipofuscinosis. Biochem. Biophys. Res. Commun. 268 (2000) 904-908. [PMID: 10679303]
4. Junaid, M.A., Wu, G.X. and Pullarkat, R.K. Purification and characterization of bovine brain lysosomal pepstatin-insensitive proteinase, the gene product deficient in the human late-infantile neuronal ceroid lipofuscinosis. J. Neurochem. 74 (2000) 287-294. [PMID: 10617131]
5. Lin, L., Sohar, I., Lackland, H. and Lobel, P. The human CLN2 protein/tripeptidyl-peptidase I is a serine protease that autoactivates at acidic pH. J. Biol. Chem. 276 (2001) 2249-2255. [PMID: 11054422]
Accepted name: tripeptidyl-peptidase II
Reaction: Release of an N-terminal tripeptide from a polypeptide
Other names: tripeptidyl aminopeptidase; tripeptidyl peptidase; tripeptidyl aminopeptidase II; tripeptidyl peptidase II; TPP
Comments: A cytosolic enzyme In peptidase family S8 (subtilisin family). Active at neutral pH. Inhibited by diisopropyl fluorophosphate. Formerly included in EC 3.4.14.8
Links to other databases: BRENDA, EXPASY, KEGG, MEROPS, Metacyc, PDB, CAS registry number: 101149-94-4
References
1. Bålöw, R.-M., Ragnarsson, U. and Zetterqvist, Ö. Tripeptidyl aminopeptidase in the extralysosomal fraction of rat liver. J. Biol. Chem. 258 (1983) 11622-11628. [PMID: 6352701]
2. Bålöw, R.-M., Tomkinson, B., Ragnarsson, U. and Zetterqvist, Ö. Purification, substrate specificity, and classification of tripeptidyl peptidase II. J. Biol. Chem. 261 (1986) 2409-2417. [PMID: 3511062]
3. Tomkinson, B. and Zetterqvist, Ö. Immunological cross-reactivity between human tripeptidyl peptidase II and fibronectin. Biochem. J. 267 (1990) 149-154. [PMID: 1691635]
Accepted name: Xaa-Pro dipeptidyl-peptidase
Reaction: Hydrolyses Xaa-Pro bonds to release unblocked, N-terminal dipeptides from substrates including Ala-Prop-nitroanilide and (sequentially) Tyr-ProPhe-ProGly-ProIle
Other names: X-prolyl dipeptidyl aminopeptidase; PepX; X-prolyl dipeptidyl peptidase; X-Pro dipeptidyl-peptidase
Comments: The intracellular enzyme from Lactococcus lactis (190-kDa) is the type example of peptidase family S15. The reaction is similar to that catalysed by dipeptidyl-peptidase IV of animals
Links to other databases: BRENDA, EXPASY, KEGG, MEROPS, Metacyc, PDB, CAS registry number: 54249-88-6
References
1. Zevaco, C., Monnet, V. and Gripon, J.-C. Intracellular X-prolyl dipeptidyl peptidase from Lactococcus lactis spp. lactis: purification and properties. J. Appl. Bacteriol. 68 (1990) 357-366
2. Meyer-Barton, E.C., Klein, J.R., Imam, M. and Plapp, R. Cloning and sequence analysis of the X-prolyl-dipeptidyl-aminopeptidase gene (pepX) from Lactobacillus delbrückii ssp. lactis DSM7290. Appl. Microbiol. Biotechnol. 40 (1993) 82-89. [PMID: 7765315]
3. Habibi-Najafi, M.B. and Lee, B.H. Purification and characterization of X-prolyl dipeptidyl peptidase from Lactobacillus casei subsp. casei LLG. Appl. Microbiol. Biotechnol. 42 (1994) 280-286. [PMID: 7765768]
4. Chich, J.-F., Gripon, J.-C. and Ribadeau-Dumas, B. Preparation of bacterial X-prolyl dipeptidyl aminopeptidase and its stabilization by organic cosolvents. Anal. Biochem. 224 (1995) 245-249. [PMID: 7710078]
5. Chich, J.-F., Chapot-Chartier, M.P., Ribadeau-Dumas, B. and Gripon, J.-C. Identification of the active site serine of the X-prolyl aminopeptidase from Lactococcus lactis. FEBS Lett. 314 (1995) 139-142
Accepted name: Xaa-Xaa-Pro tripeptidyl-peptidase
Reaction: Hydrolysis of Xaa-Xaa-ProYaa- releasing the N-terminal tripeptide of a peptide with Pro as the third residue (position P1) and where Yaa is not proline
Other name(s): prolyltripeptidyl amino peptidase; prolyl tripeptidyl peptidase; prolyltripeptidyl aminopeptidase; PTP-A; TPP
Comments: This cell-surface-associated serine exopeptidase is found in the Gram-negative, anaerobic bacterium Porphyromonas gingivalis, which has been implicated in adult periodontal disease [1]. The enzyme releases tripeptides from the free amino terminus of peptides and small proteins, such as interleukin 6. The enzyme possesses an absolute requirement for a proline residue at the P1 position but is completely inactivated by a proline residue at the P1' position [1]. The size of the peptide does not affect the rate of reaction [1].
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, PDB, CAS registry number:
References:
1. Banbula, A., Mak, P., Bugno, M., Silberring, J., Dubin, A., Nelson, D., Travis, J. and Potempa, J. Prolyl tripeptidyl peptidase from Porphyromonas gingivalis. A novel enzyme with possible pathological implications for the development of periodontitis. J Biol Chem 274 (1999) 9246-9252. [PMID: 10092598]
2. Fujimura, S., Ueda, O., Shibata, Y. and Hirai, K. Isolation and properties of a tripeptidyl peptidase from a periodontal pathogen Prevotella nigrescens. FEMS Microbiol. Lett. 219 (2003) 305-309. [PMID: 12620636]
Accepted name: γ-D-glutamyl-L-lysine dipeptidyl-peptidase
Reaction: The enzyme releases L-Ala-γ-D-Glu dipeptides from cell wall peptides via cleavage of an L-Ala-γ-D-Glu┼L-Lys bond.
Other name(s): YkfC
Comments: The enzyme, characterized from the bacterium Bacillus subtilis, is involved in the recycling of the murein peptide.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number:
References:
1. Schmidt, D.M., Hubbard, B.K. and Gerlt, J.A. Evolution of enzymatic activities in the enolase superfamily: functional assignment of unknown proteins in Bacillus subtilis and Escherichia coli as L-Ala-D/L-Glu epimerases. Biochemistry 40 (2001) 15707-15715. [PMID: 11747447]
2. Xu, Q., Abdubek, P., Astakhova, T., Axelrod, H.L., Bakolitsa, C., Cai, X., Carlton, D., Chen, C., Chiu, H.J., Chiu, M., Clayton, T., Das, D., Deller, M.C., Duan, L., Ellrott, K., Farr, C.L., Feuerhelm, J., Grant, J.C., Grzechnik, A., Han, G.W., Jaroszewski, L., Jin, K.K., Klock, H.E., Knuth, M.W., Kozbial, P., Krishna, S.S., Kumar, A., Lam, W.W., Marciano, D., Miller, M.D., Morse, A.T., Nigoghossian, E., Nopakun, A., Okach, L., Puckett, C., Reyes, R., Tien, H.J., Trame, C.B., van den Bedem, H., Weekes, D., Wooten, T., Yeh, A., Hodgson, K.O., Wooley, J., Elsliger, M.A., Deacon, A.M., Godzik, A., Lesley, S.A. and Wilson, I.A. Structure of the γ-D-glutamyl-L-diamino acid endopeptidase YkfC from Bacillus cereus in complex with L-Ala-γ-D-Glu: insights into substrate recognition by NlpC/P60 cysteine peptidases. Acta Crystallogr. Sect. F Struct. Biol. Cryst. Commun. 66 (2010) 1354-1364. [PMID: 20944232]
Accepted name: [mycofactocin precursor peptide] peptidase
Reaction: C-terminal [mycofactocin precursor peptide]-glycyl-3-amino-5-[(4-hydroxyphenyl)methyl]-4,4-dimethylpyrrolidin-2-one + H2O = C-terminal [mycofactocin precursor peptide]-glycine + 3-amino-5-[(4-hydroxyphenyl)methyl]-4,4-dimethylpyrrolidin-2-one
Glossary: 3-amino-5-[(4-hydroxyphenyl)methyl]-4,4-dimethylpyrrolidin-2-one = AHDP
Other name(s): mftE (gene name)
Systematic name: C-terminal [mycofactocin precursor peptide]-glycyl-3-amino-5-[(4-hydroxyphenyl)methyl]-4,4-dimethylpyrrolidin-2-one 3-amino-5-[(4-hydroxyphenyl)methyl]-4,4-dimethylpyrrolidin-2-one hydrolyase
Comments: Requires Fe2+ ad Zn2+. The enzyme participates in the biosynthesis of the enzyme cofactor mycofactocin. It catalyses cleavage of the mycofactocin precursor peptide following its modification by MftC to liberate its final two residues, which consist of a cross-linked valine-tyramine dipeptide.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:
References:
1. Bruender, N.A. and Bandarian, V. The creatininase homolog MftE from Mycobacterium smegmatis catalyzes a peptide cleavage reaction in the biosynthesis of a novel ribosomally synthesized post-translationally modified peptide (RiPP). J. Biol. Chem. 292 (2017) 4371-4381. [PMID: 28077628]
2. Ayikpoe, R., Salazar, J., Majestic, B. and Latham, J.A. Mycofactocin biosynthesis proceeds through 3-amino-5-[(p-hydroxyphenyl)methyl]-4,4-dimethyl-2-pyrrolidinone (AHDP); direct observation of MftE specificity toward MftA. Biochemistry 57 (2018) 5379-5383. [PMID: 30183269]
EC 3.4.15.1 peptidyl-dipeptidase A
EC 3.4.15.2 now EC 3.4.19.2
EC 3.4.15.3 deleted, included in EC 3.4.15.5
EC 3.4.15.4 peptidyl-dipeptidase B
EC 3.4.15.5 peptidyl-dipeptidase Dcp
EC 3.4.15.6 cyanophycinase
Accepted name: peptidyl-dipeptidase A
Reaction: Release of a C-terminal dipeptide, oligopeptide┼Xaa-Yaa, when Xaa is not Pro, and Yaa is neither Asp nor Glu. Thus, conversion of angiotensin I to angiotensin II, with increase in vasoconstrictor activity, but no action on angiotensin II
Glossary: captopril = (2S)-1-(2-methyl-3-sulfanylpropanoyl)-L-proline
Other name(s): dipeptidyl carboxypeptidase I; peptidase P; dipeptide hydrolase (ambiguous); peptidyl dipeptidase; angiotensin converting enzyme; kininase II; angiotensin I-converting enzyme; carboxycathepsin; dipeptidyl carboxypeptidase; peptidyl dipeptidase I; peptidyl-dipeptide hydrolase; peptidyldipeptide hydrolase; endothelial cell peptidyl dipeptidase; ACE; peptidyl dipeptidase-4; PDH; peptidyl dipeptide hydrolase; DCP
Comments: A Cl–-dependent, zinc glycoprotein that is generally membrane-bound. A potent inhibitor is captopril. Important in elevation of blood pressure, through formation of angiotensin II (vasoconstrictor) and destruction of bradykinin (vasodilator). Two molecular forms exist in mammalian tissues, a widely-distributed somatic form of 150- to 180-kDa that contains two non-identical catalytic sites, and a testicular form of 90- to 100-kDa that contains only a single catalytic site. Type example of peptidase family M2
Links to other databases:
BRENDA,
EXPASY,
KEGG,
MEROPS,
Metacyc,
PDB,
CAS registry number: 9015-82-1
References:
1. Soubrier, F., Alhenc-Gelas, F., Hubert, C., Allegrini, J., John, M., Tregear, G. and Corvol, P. Two putative active centers in human angiotensin I-converting enzyme revealed by molecular cloning. Proc. Natl. Acad. Sci. USA 85 (1988) 9386-9390. [PMID: 2849100]
2. Ehlers, M.R.W., Fox, E.A., Strydom, D.J. and Riordan, J.F. Molecular cloning of human testicular angiotensin-converting enzyme: the testis enzyme is identical to the C-terminal half of endothelial angiotensin-converting enzyme. Proc. Natl. Acad. Sci. USA 86 (1989) 7741-7745. [PMID: 2554286]
3. Wei, L., Clauser, E., Alhenc-Gelas, F. and Corvol, P. The two homologous domains of human angiotensin I-converting enzyme interact differently with competitive inhibitors. J. Biol. Chem. 267 (1992) 13398-13405. [PMID: 1320019]
4. Corvol, P., Williams, T.A. and Soubrier, F. Peptidyl dipeptidase A: angiotensin I-converting enzyme. Methods Enzymol. 248 (1995) 283-305. [PMID: 7674927]
[EC 3.4.15.2 Transferred entry: now EC 3.4.19.2 - peptidyl-glycinamidase (EC 3.4.15.2 created 1978, deleted 1981)]
[EC 3.4.15.3 Transferred entry: now EC 3.4.15.5 - peptidyl-dipeptidase Dcp (EC 3.4.15.3 created 1981, modified 1989, deleted 1996)]
Accepted name: peptidyl-dipeptidase B
Reaction: Release of a C-terminal dipeptide or exceptionally a tripeptide
Other names: dipeptidyl carboxyhydrolase; atriopeptin convertase; atrial di-(tri)peptidyl carboxyhydrolase; peptidyldipeptidase B; atrial dipeptidyl carboxyhydrolase; atrial peptide convertase
Comments: A membrane-bound, zinc metallopeptidase located in mammalian atrial, but not ventricular, myocytes. Although it is capable of converting the 126-residue atriopeptin III directly to atriopeptin I by releasing a C-terminal tripeptide Phe-Arg-Tyr, it is generally restricted to the release of dipeptides. In contrast to peptidyl-dipeptidase A (EC 3.4.15.1) it displays no Cl- dependence and shows no action on angiotensin I. Conversely, peptidyl-dipeptidase A is unable to release Phe-Arg from the C-terminus of atriopeptin II
Links to other databases:
BRENDA,
EXPASY,
KEGG,
MEROPS,
Metacyc,
CAS registry number: 147014-93-5
References
1. Harris, R.B. and Wilson, I.B. Atrial tissue contains a metallo dipeptidyl carboxyhydrolase not present in ventricular tissue: partial purification and characterization. Arch. Biochem. Biophys. 233 (1984) 667-675. [PMID: 6385859]
2. Harris, R.B. and Wilson, I.B. Conversion of atriopeptin II to atriopeptin I by atrial dipeptidyl carboxy hydrolase. Peptides (Fayetteville) 6 (1985) 393-396. [PMID: 2999723]
3. Soler, D.F. and Harris, R.B. Continuous fluorogenic substrates for atrial dipeptidyl carboxyhydrolase. Importance of Ser in the P1 position. Int. J. Peptide Protein Res. 32 (1988) 35-40. [PMID: 3146555]
4. Soler, D.F. and Harris, R.B. Atrial dipeptidyl carboxyhydrolase is a zinc-metallo proteinase which possesses tripeptidyl carboxyhydrolase activity. Peptides (Fayetteville) 10 (1989) 63-68. [PMID: 2501770]
Accepted name: peptidyl-dipeptidase Dcp
Reaction: Hydrolysis of unblocked, C-terminal dipeptides from oligopeptides, with broad specificity. Does not hydrolyse bonds in which P1' is Pro, or both P1 and P1' are Gly
Other names: dipeptidyl carboxypeptidase (Dcp); dipeptidyl carboxypeptidase
Comments: Known from Escherichia coli and Salmonella typhimurium. A zinc metallopeptidase In peptidase family M3 (thimet oligopeptidase family). Ac-Ala
Links to other databases:
BRENDA,
EXPASY,
KEGG,
MEROPS,
Metacyc,
PDB,
CAS registry number: 395642-28-1
References
1. Yaron, A. Dipeptidyl carboxypeptidase from Escherichia coli. Methods Enzymol. 45 (1976) 599-610. [PMID: 13271]
2. Henrich, B., Becker, S., Schroeder, U. and Plapp, R. dcp Gene of Escherichia coli: cloning, sequencing, transcript mapping, and characterization of the gene product. J. Bacteriol. 175 (1993) 7290-7300. [PMID: 8226676]
3. Conlin, C.A. and Miller, C.G. Oligopeptidase A and peptidyl-dipeptidase of Escherichia and Salmonella. Methods Enzymol. 248 (1995) 567-579. [PMID: 7674945]
Accepted name: cyanophycinase
Reaction: [L-Asp(4-L-Arg)]n + H2O = [L-Asp(4-L-Arg)]n-1 + L-Asp(4-L-Arg)
For diagram click here.
Glossary: cyanophycin = [L-Asp(4-L-Arg)]n = N-β-aspartylarginine = [L-4-(L-arginin-2-N-yl)aspartic acid]n = poly{N4-[(1S)-1-carboxy-4-guanidinobutyl]-L-asparagine}
Other name(s): cyanophycin degrading enzyme; β-Asp-Arg hydrolysing enzyme; CGPase; CphB; CphE; cyanophycin granule polypeptidase; extracellular CGPase
Comments: The enzyme is highly specific for the branched polypeptide cyanophycin and does not hydrolyse poly-L-aspartate or poly-L-arginine [3]. A serine-type exopeptidase that belongs in peptidase family S51.
Links to other databases:
BRENDA,
EXPASY,
KEGG,
MEROPS,
Metacyc,
PDB,
CAS registry number:
References:
1. Obst, M., Krug, A., Luftmann, H. and Steinbüchel, A. Degradation of cyanophycin by Sedimentibacter hongkongensis strain KI and Citrobacter amalonaticus strain G isolated from an anaerobic bacterial consortium. Appl. Environ. Microbiol. 71 (2005) 3642-3652. [PMID: 16000772]
2. Obst, M., Oppermann-Sanio, F.B., Luftmann, H. and Steinbüchel, A. Isolation of cyanophycin-degrading bacteria, cloning and characterization of an extracellular cyanophycinase gene (cphE) from Pseudomonas anguilliseptica strain BI. The cphE gene from P. anguilliseptica BI encodes a cyanophycin-hydrolyzing enzyme. J. Biol. Chem. 277 (2002) 25096-25105. [PMID: 11986309]
3. Richter, R., Hejazi, M., Kraft, R., Ziegler, K. and Lockau, W. Cyanophycinase, a peptidase degrading the cyanobacterial reserve material multi-L-arginyl-poly-L-aspartic acid (cyanophycin): molecular cloning of the gene of Synechocystis sp. PCC 6803, expression in Escherichia coli, and biochemical characterization of the purified enzyme. Eur. J. Biochem. 263 (1999) 163-169. [PMID: 10429200]
Ala-Ala is a good test substrate [3]. Inhibited by captopril, as is peptidyl-dipeptidase A. Formerly EC 3.4.15.3, and included in EC 3.4.15.1, peptidyl-dipeptidase A."
Continued with EC 3.4.16 to EC 3.4.20.
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