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UniProtKB:Accession Number | Q01693 |
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Entry name | AMPX_VIBPR |
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Activity | Release of an N-terminal amino acid, preferentially leucine, but not glutamic or aspartic acids. |
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Subunit |
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Subcellular location | Secreted. |
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Cofactor | Binds 2 zinc ions per subunit. |
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References for Catalytic Mechanism | References | Sections | No. of steps in catalysis |
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[4] | p.396-397 |
| [5] | Fig.7, p.4283-4285 | 4 | [6] | p.9050-9053 |
| [10] | Fig.10, p.7042-7045 | 4 | [12] | p.1196-1199 |
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references | [1] |
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PubMed ID | 8357796 |
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Journal | Biochemistry |
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Year | 1993 |
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Volume | 32 |
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Pages | 8465-78 |
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Authors | Kim H, Lipscomb WN |
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Title | X-ray crystallographic determination of the structure of bovine lens leucine aminopeptidase complexed with amastatin: formulation of a catalytic mechanism featuring a gem-diolate transition state. |
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[2] |
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Comments | X-ray crystallography (1.8 Angstroms) |
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Medline ID | 94373500 |
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PubMed ID | 8087555 |
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Journal | Structure |
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Year | 1994 |
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Volume | 2 |
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Pages | 283-91 |
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Authors | Chevrier B, Schalk C, D'Orchymont H, Rondeau JM, Moras D, Tarnus C |
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Title | Crystal structure of Aeromonas proteolytica aminopeptidase: a prototypical member of the co-catalytic zinc enzyme family. |
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Related PDB | 1amp |
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Related UniProtKB | Q01693 |
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[3] |
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PubMed ID | 7578088 |
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Journal | Biochemistry |
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Year | 1995 |
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Volume | 34 |
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Pages | 14792-800 |
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Authors | Strater N, Lipscomb WN |
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Title | Two-metal ion mechanism of bovine lens leucine aminopeptidase: active site solvent structure and binding mode of L-leucinal, a gem-diolate transition state analogue, by X-ray crystallography. |
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[4] |
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Comments | X-ray crystallography complex with inhibitor |
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Medline ID | 96215434 |
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PubMed ID | 8647077 |
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Journal | Eur J Biochem |
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Year | 1996 |
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Volume | 237 |
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Pages | 393-8 |
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Authors | Chevrier B, D'Orchymont H, Schalk C, Tarnus C, Moras D |
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Title | The structure of the Aeromonas proteolytica aminopeptidase complexed with a hydroxamate inhibitor. Involvement in catalysis of Glu151 and two zinc ions of the co-catalytic unit. |
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Related PDB | 1igb |
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Related UniProtKB | Q01693 |
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[5] |
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Comments | mechanistic studies, catalysis |
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PubMed ID | 9100023 |
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Journal | Biochemistry |
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Year | 1997 |
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Volume | 36 |
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Pages | 4278-86 |
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Authors | Chen G, Edwards T, D'souza VM, Holz RC |
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Title | Mechanistic studies on the aminopeptidase from Aeromonas proteolytica: a two-metal ion mechanism for peptide hydrolysis. |
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[6] |
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Comments | X-ray crystallography (1.9 Angstroms) |
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PubMed ID | 10413478 |
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Journal | Biochemistry |
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Year | 1999 |
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Volume | 38 |
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Pages | 9048-53 |
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Authors | De Paola CC, Bennett B, Holz RC, Ringe D, Petsko GA |
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Title | 1-Butaneboronic acid binding to Aeromonas proteolytica aminopeptidase: a case of arrested development. |
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Related PDB | 1cp6 |
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[7] |
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Comments | inhibition, catalysis |
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PubMed ID | 10471294 |
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Journal | Biochemistry |
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Year | 1999 |
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Volume | 38 |
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Pages | 11433-9 |
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Authors | Ustynyuk L, Bennett B, Edwards T, Holz RC |
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Title | Inhibition of the aminopeptidase from Aeromonas proteolytica by aliphatic alcohols. Characterization of the hydrophobic substrate recognition site. |
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[8] |
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PubMed ID | 10500145 |
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Journal | Proc Natl Acad Sci U S A |
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Year | 1999 |
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Volume | 96 |
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Pages | 11151-5 |
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Authors | Strater N, Sun L, Kantrowitz ER, Lipscomb WN |
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Title | A bicarbonate ion as a general base in the mechanism of peptide hydrolysis by dizinc leucine aminopeptidase. |
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[9] |
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Comments | inhibition |
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PubMed ID | 10569943 |
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Journal | Biochemistry |
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Year | 1999 |
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Volume | 38 |
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Pages | 15587-96 |
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Authors | Huntington KM, Bienvenue DL, Wei Y, Bennett B, Holz RC, Pei D |
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Title | Slow-binding inhibition of the aminopeptidase from Aeromonas proteolytica by peptide thiols: synthesis and spectroscopic characterization. |
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[10] |
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Comments | X-ray crystallography (2.1 Angstroms) |
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PubMed ID | 11401547 |
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Journal | Biochemistry |
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Year | 2001 |
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Volume | 40 |
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Pages | 7035-46 |
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Authors | Stamper C, Bennett B, Edwards T, Holz RC, Ringe D, Petsko G |
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Title | Inhibition of the aminopeptidase from Aeromonas proteolytica by L-leucinephosphonic acid. Spectroscopic and crystallographic characterization of the transition state of peptide hydrolysis. |
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Related PDB | 1ft7 |
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[11] |
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Comments | X-ray crystallography (1.53-1.80 Angstroms) |
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PubMed ID | 11484227 |
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Journal | Proteins |
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Year | 2001 |
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Volume | 44 |
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Pages | 490-504 |
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Authors | Gilboa R, Spungin-Bialik A, Wohlfahrt G, Schomburg D, Blumberg S, Shoham G |
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Title | Interactions of Streptomyces griseus aminopeptidase with amino acid reaction products and their implications toward a catalytic mechanism. |
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[12] |
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PubMed ID | 11743734 |
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Journal | J Mol Biol |
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Year | 2001 |
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Volume | 314 |
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Pages | 1191-207 |
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Authors | Wouters MA, Husain A |
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Title | Changes in zinc ligation promote remodeling of the active site in the zinc hydrolase superfamily. |
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comments | This enzyme belongs to the peptidase family-M28A. The paper [4] suggested that Glu151 could play the catalytic role as a general base in the catalysis. According to the literature [5], as for the metal-bound water, the higher the coordination number, the higher the pKa. Furthermore, as the number of carboxylate ligands to a Zn(II) ion increases, the pKa becomes the higher [5]. Thus, Glu151 facilitate the deprotonation of the terminal water molecule to the nucleophilic hydroxo moiety, which can attack the activated scissile carbonyl carbon of the peptide substrate, forming a gem-diolate intermediate complex that is stabilized by coordination of both oxygen atoms to the dizinc(II) center. In addition, at the next stage, Glu151 can donate an additional proton to the penultimate amino nitrogen recovering its ionized state. According to the paper [12], the transition state is a non-covalently bound tetrahedral gem-diolate, which is opposed to a covalent acyl anhydride transition state as found in serine proteases.
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created | updated |
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2002-09-27 | 2009-02-26 |
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