Enzyme Nomenclature. Recommendations 1992

Continued from Transferred entries


EC 3.4.11 to EC 3.4.15

Sections

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


EC 3.4.11 Aminopeptidases

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


Entries

EC 3.4.11.1

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]

[EC 3.4.11.1 created 1961 as EC 3.4.1.1, transferred 1972 to EC 3.4.11.1]

EC 3.4.11.2

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]

[EC 3.4.11.2 created 1961 as EC 3.4.1.2, transferred 1972 to EC 3.4.11.2 (EC 3.4.13.6 created 1961 as EC 3.4.3.5, transferred 1972 to EC 3.4.13.6, incorporated 1997)]

EC 3.4.11.3

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

[EC 3.4.11.3 created 1972]

EC 3.4.11.4

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]

[EC 3.4.11.4 created 1961 as EC 3.4.1.3, transferred 1972 to EC 3.4.11.4]

EC 3.4.11.5

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]

[EC 3.4.11.5 created 1965 as EC 3.4.1.4, transferred 1972 to EC 3.4.11.5]

EC 3.4.11.6

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]

[EC 3.4.11.6 created 1972, modified 1997]

EC 3.4.11.7

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 3.4.11.7 created 1972]

[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)]

EC 3.4.11.9

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]

[EC 3.4.11.9 created 1972]

EC 3.4.11.10

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 3.4.11.10 created 1972]

[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)]

EC 3.4.11.13

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]

[EC 3.4.11.13 created 1978]

EC 3.4.11.14

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]

[EC 3.4.11.14 created 1978]

EC 3.4.11.15

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]

[EC 3.4.11.15 created 1989, modified 1997]

EC 3.4.11.16

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]

[EC 3.4.11.16 created 1989]

EC 3.4.11.17

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, 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

[EC 3.4.11.17 created 1989]

EC 3.4.11.18

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]

[EC 3.4.11.18 created 1990]

EC 3.4.11.19

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]

[EC 3.4.11.19 created 1993]

EC 3.4.11.20

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]

[EC 3.4.11.20 created 1995]

EC 3.4.11.21

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]

[EC 3.4.11.21 created 2000]

EC 3.4.11.22

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]

[EC 3.4.11.22 created 1997]

EC 3.4.11.23

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, 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]

[EC 3.4.11.23 created 2003]

EC 3.4.11.24

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]

[EC 3.4.11.24 created 2008]

EC 3.4.11.25

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]

[EC 3.4.11.25 created 2011]

EC 3.4.11.26

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, 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]

[EC 3.4.11.26 created 2011]


3.4.13 Dipeptidases

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


Entries

[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)]

EC 3.4.13.4

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, 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]

[EC 3.4.13.4 created 1972]

EC 3.4.13.5

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 3.4.13.5 created 1961 as EC 3.4.3.4, transferred 1972 to EC 3.4.13.5, modified 1981 (EC 3.5.1.34 created 1972, incorporated 1981)]

[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)]

EC 3.4.13.7

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 3.4.13.7 created 1972]

[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)]

EC 3.4.13.9

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 3.4.13.9 created 1961 as EC 3.4.3.7, transferred 1972 to EC 3.4.13.9]

[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)]

EC 3.4.13.12

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 3.4.13.12 created 1976]

[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)]

EC 3.4.13.17

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]

[EC 3.4.13.17 created 1990]

EC 3.4.13.18

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, Metacyc, 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

[EC 3.4.13.18 created 1961 as EC 3.4.3.1 and EC 3.4.3.2, transferred 1972 to EC 3.4.13.1 and EC 3.4.13.2, transferred 1978 to EC 3.4.13.11, part transferred 1992 to EC 3.4.13.18, modified 2000 (EC 3.4.13.15 created 1989, incorporated 1992)]

EC 3.4.13.19

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]

[EC 3.4.13.19 created 1961 as EC 3.4.3.1 and EC 3.4.3.2, transferred 1972 to EC 3.4.13.1 and EC 3.4.13.2, transferred 1978 to EC 3.4.13.11, part transferred 1992 to EC 3.4.13.19, modified 2011]

EC 3.4.13.20

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, 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]

[EC 3.4.13.20 created 1992]

EC 3.4.13.21

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]

[EC 3.4.13.21 created 2001]

EC 3.4.13.22

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]

[EC 3.4.13.22 created 2006]


EC 3.4.14 Dipeptidyl-Peptidases and Tripeptidyl-Peptidases

Contents

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


Entries

EC 3.4.14.1

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

[EC 3.4.14.1 created 1961 as EC 3.4.4.9, transferred 1972 to EC 3.4.14.1]

EC 3.4.14.2

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 3.4.14.2 created 1978]

[EC 3.4.14.3 Transferred entry: now EC 3.4.19.1 - Acylaminoacyl-peptidase (EC 3.4.14.3 created 1978, deleted 1981)]

EC 3.4.14.4

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]

[EC 3.4.14.4 created 1981, modified 2001]

EC 3.4.14.5

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]

[EC 3.4.14.5 created 1981, modified 1996]

EC 3.4.14.6

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 3.4.14.6 created 1989]

[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)]

EC 3.4.14.9

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]

[EC 3.4.14.9 created 1992 (part of EC 3.4.14.8 created 1989, incorporated 1992), modified 2000, modified 2001, modified 2003]

EC 3.4.14.10

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]

[EC 3.4.14.10 created 1992 (part of EC 3.4.14.8 created 1989, incorporated 1992)]

EC 3.4.14.11

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

[EC 3.4.14.11 created 1996]

EC 3.4.14.12

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]

[EC 3.4.14.12 created 2006]

EC 3.4.14.13

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, 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]

[EC 3.4.14.13 created 2015]


EC 3.4.15 Peptidyl-Dipeptidases

Contents

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


Entries

EC 3.4.15.1

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-(3-mercapto-2-methylpropanoyl)-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 3.4.15.1 created 1972, modified 1981, modified 1989, modified 1996, modified 2011]

[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)]

EC 3.4.15.4

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]

[EC 3.4.15.4 created 1992]

EC 3.4.15.5

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-AlaAla-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."

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]

[EC 3.4.15.5 created 1981 as EC 3.4.15.3, modified 1989, transferred 1996 to EC 3.4.15.5]

EC 3.4.15.6

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]

[EC 3.4.15.6 created 2007]


Continued with EC 3.4.16 to EC 3.4.20.
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