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Overview for MACiE Entry M0171

Version history

General Information

EC Number: 3.4.17.1 (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).

Catalytic CATH Codes:

Display structure information

Overall Reaction:

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protein
C00017
CHEBI:33711
water
C00001
CHEBI:15377
proton
C00080
CHEBI:24636
amino acid
C00045
CHEBI:59814
protein
C00017
CHEBI:33711

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 [1].


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Stepwise Description of the Reaction

Step 1Glu270 deprotonates the zinc activated water molecule. This activated hydroxide then attacks the carbonyl carbon of the peptide bond in a nucleophilic addition.
Step 2The oxyanion initiates an elimination that cleaves the peptide bond. The amine side of the bond then deprotonates the carboxylic side.
Step 3Water deprotonates Glu270, regenerating the active site.

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Catalytic Residues Involved

Type Number Chain Location of Function
Arg 127 A Side Chain
Glu 270 A Side Chain

Metal Cofactors for M0171

Type Het group Number Chain
zinc ZN 1308 A Overview

References

  1. 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.
  2. D. W. Christianson et al. (1989), Acc. Chem. Res., 22, 62-69. Carboxypeptidase A.
  3. 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.
    Medline: 3463986
  4. 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.
    Medline: 2386784

Homologue information for M0171 (1m4l)

CSA Homologues

MACiE Homologues (within the PDB)

MACiE Homologues (within UniprotKB/SwissProt)



Entries with at least one Catalytic CATH code in common (different mechanisms):

MACiE Entry Enzyme Name
EC Number
PDB code CATH code Composite
Reaction Similarity
Catalytic Machinery
Similarity
M0167 bacterial leucyl aminopeptidase
3.4.11.10
1lok 3.40.630.10
0.6250.4652Compare

Links to this entry in other databases

Link to EC-PDB-SUM Link to PDB-SUM Link to RCSB PDB Link to PDBe Link to CSA
Link to MetaCyc Link to KEGG Link to BRENDA Link to ExplorENZ
Link to EzCatDB

GOA logo
metallocarboxypeptidase activity (molecular function)
extracellular region (cellular component)
extracellular space (cellular component)
proteolysis (biological process)
peptidase activity (molecular function)
metallopeptidase activity (molecular function)
zinc ion binding (molecular function)
metal ion binding (molecular function)
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