Overview for MACiE Entry M0171
EC Number: 188.8.131.52 (A member of the Hydrolases, Acting on peptide bonds (peptidases), Metallocarboxypeptidases)
Enzyme Name: carboxypeptidase A
Biological Species: Bos taurus (Cow)
Catalytic Chain UniprotKB Accession Codes:
Representative PDB Code: 1m4l - STRUCTURE OF NATIVE CARBOXYPEPTIDASE A AT 1.25 RESOLUTION (Resolution = 1.25 Å).
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Overall Comment: Several alternative catalytic pathways have been suggested for this enzyme which may be divided into two major groups. The first of which starts from direct nucleophilic attack on the peptide carbonyl by Glu270. The second pathway involves the general acid/general base Mechanism in which the water that attacks the peptide carbonyl is initially activated by the Zn/Glu270 system or by the C terminal carboxylic group of the substrate. We show the general acid/general base mechanism in which the water is activated by Zn/Glu270. This is supported although not conclusively in ref .
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Stepwise Description of the Reaction
|Step 1||Glu270 deprotonates the zinc activated water molecule. This activated hydroxide then attacks the carbonyl carbon of the peptide bond in a nucleophilic addition.|
|Step 2||The oxyanion initiates an elimination that cleaves the peptide bond. The amine side of the bond then deprotonates the carboxylic side.|
|Step 3||Water deprotonates Glu270, regenerating the active site.|
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Catalytic Residues Involved
||Location of Function
Metal Cofactors for M0171
- A. Kilshtain-Vardi et al. (2002), Int. J. Quant. Chem., 88, 87-98. Mechanism of action of zinc proteinases: A MNDO/d/H study of alternative general-acid general-base catalytic pathways for carboxypeptidase-A.
- D. W. Christianson et al. (1989), Acc. Chem. Res., 22, 62-69. Carboxypeptidase A.
- D. W. Christianson et al. (1986), Proc. Natl Acad. Sci. USA, 83, 7568-7572. X-ray crystallographic investigation of substrate binding to carboxypeptidase A at subzero temperature.
- H. Kim et al. (1990), Biochemistry, 29, 5546-5555. Crystal structure of the complex of carboxypeptidase A with a strongly bound phosphonate in a new crystalline form: comparison with structures of other complexes.
Homologue information for M0171 (1m4l)
MACiE Homologues (within the PDB)
MACiE Homologues (within UniprotKB/SwissProt)
Entries with at least one Catalytic CATH code in common (different mechanisms):
|M0167 ||bacterial leucyl aminopeptidase |
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