DB code: D00467

RLCP classification 1.13.11110.262 : Hydrolysis
CATH domain 3.30.70.340 : Alpha-Beta Plaits
3.40.630.10 : Aminopeptidase Catalytic domain
E.C. 3.4.17.1
CSA 5cpa 1cbx
M-CSA 5cpa 1cbx
MACiE M0171

CATH domain Related DB codes (homologues)
3.40.630.10 : Aminopeptidase D00512 S00406 S00407 D00192 D00193
3.30.70.340 : Alpha-Beta Plaits D00512 D00193

Uniprot Enzyme Name
UniprotKB Protein name Synonyms MEROPS Pfam RefSeq
O97389
Carboxypeptidase A
EC 3.4.17.1
M14.024 (Metallo)
PF00246 (Peptidase_M14)
PF02244 (Propep_M14)
[Graphical View]
P09954 Carboxypeptidase A1
EC 3.4.17.1
M14.001 (Metallo)
PF00246 (Peptidase_M14)
PF02244 (Propep_M14)
[Graphical View]
NP_999409.1 (Protein)
NM_214244.1 (DNA/RNA sequence)
P00730 Carboxypeptidase A1
EC 3.4.17.1
M14.001 (Metallo)
PF00246 (Peptidase_M14)
PF02244 (Propep_M14)
[Graphical View]
NP_777175.1 (Protein)
NM_174750.2 (DNA/RNA sequence)

KEGG enzyme name
carboxypeptidase A
carboxypolypeptidase
pancreatic carboxypeptidase A
tissue carboxypeptidase A

UniprotKB: Accession Number Entry name Activity Subunit Subcellular location Cofactor
O97389 O97389_HELAM
P09954 CBPA1_PIG Release of a C-terminal amino acid, but little or no action with -Asp, -Glu, -Arg, -Lys or -Pro. Monomer. Secreted. Binds 1 zinc ion per subunit.
P00730 CBPA1_BOVIN Release of a C-terminal amino acid, but little or no action with -Asp, -Glu, -Arg, -Lys or -Pro. Monomer. The zymogen is secreted as a ternary complex composed of procarboxypeptidase A, chymotrypsinogen C and proproteinase E. Secreted, extracellular space. Binds 1 zinc ion per subunit.

KEGG Pathways
Map code Pathways E.C.

Compound table
Cofactors Substrates Products Intermediates
KEGG-id C00038 C00017 C00012 C00001 C00012 C00151
E.C. (gem-diolate) transition-state
Compound Zinc Protein Peptide H2O Peptide L-Amino acid tetrahedral
Type heavy metal peptide/protein peptide/protein H2O peptide/protein amino acids
ChEBI 29105
15377
PubChem 32051
22247451
962
1jqgA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1pcaA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1pytA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1jqgA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:_ZN Unbound Unbound Unbound Unbound
1pcaB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:_ZN Unbound Unbound Unbound Bound:VAL
1arlA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1armA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Analogue:_HG_308 Unbound Unbound Unbound Unbound Transition-state-analogue:TRS
1bavA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:_ZN Unbound Unbound Unbound Analogue:BIP
1bavB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:_ZN Unbound Unbound Unbound Analogue:BIP
1bavC Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:_ZN Unbound Unbound Unbound Analogue:BIP
1bavD Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:_ZN Unbound Unbound Unbound Analogue:BIP
1cbxA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:_ZN Unbound Unbound Unbound Unbound Transition-state-analogue:BZS
1cpaA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:_ZN Unbound Bound:GLY-TYR (chain S) Unbound Unbound
1cpsA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:_ZN Unbound Unbound Unbound Unbound Transition-state-analogue:CPM
1cpxA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:_ZN_308 Unbound Unbound Analogue:_OH Unbound Unbound
1ee3P Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Analogue:_CD_350 Unbound Unbound Unbound Unbound
1ellP Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Analogue:_CD_350 Unbound Unbound Unbound Unbound
1elmP Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Analogue:_CD_350 Unbound Unbound Unbound Unbound
1f57A Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:_ZN Unbound Unbound Unbound Analogue:DCY
1hdqA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:_ZN Unbound Analogue:INF Unbound Unbound
1hduA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:_ZN Unbound Analogue:ING Unbound Unbound
1hduB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:_ZN Unbound Analogue:ING Unbound Unbound
1hduD Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:_ZN Unbound Analogue:ING Unbound Unbound
1hduE Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:_ZN Unbound Analogue:ING Unbound Unbound
1heeA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:_ZN Unbound Analogue:LHY Unbound Unbound
1heeB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:_ZN Unbound Analogue:LHY Unbound Unbound
1heeD Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:_ZN Unbound Analogue:LHY Unbound Unbound
1heeE Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:_ZN Unbound Analogue:LHY Unbound Unbound
1iy7A Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:_ZN Unbound Unbound Unbound Unbound Transition-state-analogue:CXA
1m4lA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:_ZN Unbound Unbound Unbound Unbound
1pytB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:_ZN Unbound Unbound Unbound Unbound
1ymeA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:_ZN Unbound Unbound Unbound Unbound
1zlhA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:_ZN_555 Unbound Unbound Analogue:LEU_74 (chain B) Unbound
2abzA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:_ZN Unbound Unbound Analogue:VAL_66 (chain C) Unbound
2abzB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:_ZN Unbound Unbound Analogue:VAL_66 (chain E) Unbound
2ctbA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:_ZN Unbound Unbound Unbound Unbound
2ctcA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:_ZN Unbound Unbound Unbound Analogue:HFA
3cpaA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:_ZN Unbound Bound:GLY-TYR (chain S) Unbound Unbound
4cpaA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:_ZN Unbound Unbound Bound:VAL_38 (chain I) Bound:GLY (chain G)
5cpaA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:_ZN Unbound Unbound Unbound Unbound
6cpaA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:_ZN Unbound Unbound Unbound Unbound Transition-state-analogue:ZAF
7cpaA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:_ZN Unbound Unbound Unbound Unbound Transition-state-analogue:FVF
8cpaA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:_ZN Unbound Unbound Unbound Unbound Transition-state-analogue:AGF

Reference for Active-site residues
resource references E.C.
Swiss-prot;P00730, P09954

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
1jqgA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1pcaA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1pytA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1jqgA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ARG 127;GLU 270 HIS 69;GLU 72;HIS 196(Zinc binding) SER 197
1pcaB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ARG 127;GLU 270 HIS 69;GLU 72;HIS 196(Zinc binding) SER 197
1arlA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ARG 127;GLU 270 HIS 69;GLU 72;HIS 196(Zinc binding) SER 197
1armA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ARG 127;GLU 270 HIS 69;GLU 72;HIS 196(Zinc binding) SER 197
1bavA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ARG 127;GLU 270 HIS 69;GLU 72;HIS 196(Zinc binding) SER 197
1bavB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ARG 127;GLU 270 HIS 69;GLU 72;HIS 196(Zinc binding) SER 197
1bavC Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ARG 127;GLU 270 HIS 69;GLU 72;HIS 196(Zinc binding) SER 197
1bavD Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ARG 127;GLU 270 HIS 69;GLU 72;HIS 196(Zinc binding) SER 197
1cbxA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ARG 127;GLU 270 HIS 69;GLU 72;HIS 196(Zinc binding) SER 197
1cpaA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ARG 127;GLU 270 HIS 69;GLU 72;HIS 196(Zinc binding) SER 197
1cpsA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ARG 127;GLU 270 HIS 69;GLU 72;HIS 196(Zinc binding) SER 197
1cpxA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ARG 127;GLU 270 HIS 69;GLU 72;HIS 196(Zinc binding) SER 197
1ee3P Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ARG 127;GLU 270 HIS 69;GLU 72;HIS 196(Zinc binding) SER 197
1ellP Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ARG 127;GLU 270 HIS 69;GLU 72;HIS 196(Zinc binding) SER 197
1elmP Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ARG 127;GLU 270 HIS 69;GLU 72;HIS 196(Zinc binding) SER 197
1f57A Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ARG 127;GLU 270 HIS 69;GLU 72;HIS 196(Zinc binding) SER 197
1hdqA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ARG 127;GLU 270 HIS 69;GLU 72;HIS 196(Zinc binding) SER 197
1hduA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ARG 127;GLU 270 HIS 69;GLU 72;HIS 196(Zinc binding) SER 197
1hduB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ARG 127;GLU 270 HIS 69;GLU 72;HIS 196(Zinc binding) SER 197
1hduD Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ARG 127;GLU 270 HIS 69;GLU 72;HIS 196(Zinc binding) SER 197
1hduE Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ARG 127;GLU 270 HIS 69;GLU 72;HIS 196(Zinc binding) SER 197
1heeA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ARG 127;GLU 270 HIS 69;GLU 72;HIS 196(Zinc binding) SER 197
1heeB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ARG 127;GLU 270 HIS 69;GLU 72;HIS 196(Zinc binding) SER 197
1heeD Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ARG 127;GLU 270 HIS 69;GLU 72;HIS 196(Zinc binding) SER 197
1heeE Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ARG 127;GLU 270 HIS 69;GLU 72;HIS 196(Zinc binding) SER 197
1iy7A Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ARG 127;GLU 270 HIS 69;GLU 72;HIS 196(Zinc binding) SER 197
1m4lA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ARG 127;GLU 270 HIS 69;GLU 72;HIS 196(Zinc binding) SER 197
1pytB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ARG 127;GLU 270 HIS 69;GLU 72;HIS 196(Zinc binding) SER 197
1ymeA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ARG 127;GLU 270 HIS 69;GLU 72;HIS 196(Zinc binding) SER 197
1zlhA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ARG 127;GLU 270 HIS 69;GLU 72;HIS 196(Zinc binding) SER 197
2abzA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ARG 127;GLU 270 HIS 69;GLU 72;HIS 196(Zinc binding) SER 197
2abzB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ARG 127;GLU 270 HIS 69;GLU 72;HIS 196(Zinc binding) SER 197
2ctbA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ARG 127;GLU 270 HIS 69;GLU 72;HIS 196(Zinc binding) SER 197
2ctcA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ARG 127;GLU 270 HIS 69;GLU 72;HIS 196(Zinc binding) SER 197
3cpaA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ARG 127;GLU 270 HIS 69;GLU 72;HIS 196(Zinc binding) SER 197
4cpaA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ARG 127;GLU 270 HIS 69;GLU 72;HIS 196(Zinc binding) SER 197
5cpaA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ARG 127;GLU 270 HIS 69;GLU 72;HIS 196(Zinc binding) SER 197
6cpaA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ARG 127;GLU 270 HIS 69;GLU 72;HIS 196(Zinc binding) SER 197
7cpaA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ARG 127;GLU 270 HIS 69;GLU 72;HIS 196(Zinc binding) SER 197
8cpaA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ARG 127;GLU 270 HIS 69;GLU 72;HIS 196(Zinc binding) SER 197

References for Catalytic Mechanism
References Sections No. of steps in catalysis
[1]
p.3877
[4]
p.495-497
[6]
p.20-24
[10]
p.7571-7572
[13]
Fig.10, p.63-69
[15]
Fig.4, p.12852 1
[17]
Fig.8, p.5551-5553
[18]
Fig.2, p.20698 2
[21]
p.8178-8179
[22]
Fig.6, p.6396-6399
[26]
[27]
p.146-150
[28]
p.576-577
[32]
p.383-384
[34]
p.4592-4594
[37]
p.2381-2382
[39]
p.8714
[47]
p.285
[48]
Fig.5, p.821
[49]
Fig.2, p.10199
[51]
p.1196-1199
[55]
Fig.8, p.497-499
[57]
p.327-332

References
[1]
Resource
Comments
Medline ID
PubMed ID 6933442
Journal Proc Natl Acad Sci U S A
Year 1980
Volume 77
Pages 3875-8
Authors Lipscomb WN
Title Carboxypeptidase A mechanisms.
Related PDB
Related UniProtKB
[2]
Resource
Comments
Medline ID
PubMed ID 7274452
Journal FEBS Lett
Year 1981
Volume 128
Pages 13-6
Authors Wicker C, Puigserver A
Title Further studies on subunit III of bovine procarboxypeptidase A. Structure and reactivity of the weakly functional active site.
Related PDB
Related UniProtKB
[3]
Resource
Comments
Medline ID
PubMed ID 7152041
Journal FEBS Lett
Year 1982
Volume 149
Pages 257-60
Authors Aviles FX, Segundo BS, Vilanova M, Cuchillo CM, Turner C
Title The activation segment of procarboxypeptidase A from porcine pancreas constitutes a folded structural domain.
Related PDB
Related UniProtKB
[4]
Resource
Comments X-ray Diffraction
Medline ID
PubMed ID 7154070
Journal J Mol Biol
Year 1982
Volume 160
Pages 475-98
Authors Rees DC, Lipscomb WN
Title Refined crystal structure of the potato inhibitor complex of carboxypeptidase A at 2.5 A resolution.
Related PDB 4cpa
Related UniProtKB
[5]
Resource
Comments X-RAY CRYSTALLOGRAPHY (1.54 ANGSTROMS).
Medline ID
PubMed ID 6887246
Journal J Mol Biol
Year 1983
Volume 168
Pages 367-87
Authors Rees DC, Lewis M, Lipscomb WN
Title Refined crystal structure of carboxypeptidase A at 1.54 A resolution.
Related PDB 5cpa
Related UniProtKB P00730
[6]
Resource
Comments
Medline ID
PubMed ID 2994404
Journal Adv Enzymol Relat Areas Mol Biol
Year 1985
Volume 57
Pages 1-84
Authors Patchett AA, Cordes EH
Title The design and properties of N-carboxyalkyldipeptide inhibitors of angiotensin-converting enzyme.
Related PDB
Related UniProtKB
[7]
Resource
Comments
Medline ID
PubMed ID 4026847
Journal Biochem Biophys Res Commun
Year 1985
Volume 130
Pages 97-103
Authors Aviles FX, Vendrell J, Burgos FJ, Soriano F, Mendez E
Title Sequential homologies between procarboxypeptidases A and B from porcine pancreas.
Related PDB
Related UniProtKB
[8]
Resource
Comments
Medline ID
PubMed ID 3636229
Journal Eur J Biochem
Year 1986
Volume 157
Pages 531-8
Authors Kerfelec B, Cambillau C, Puigserver A, Chapus C
Title The inactive subunit of ruminant procarboxypeptidase A-S6 complexes. Structural basis of inactivity and physiological role.
Related PDB
Related UniProtKB
[9]
Resource
Comments
Medline ID
PubMed ID 3783689
Journal J Mol Biol
Year 1986
Volume 189
Pages 709-10
Authors Cambillau C, Kerfelec B, Foglizzo E, Chapus C
Title Crystallization and preliminary X-ray study of subunit III of the bovine pancreatic procarboxypeptidase A-S6 ternary complex.
Related PDB
Related UniProtKB
[10]
Resource
Comments X-ray Diffraction
Medline ID
PubMed ID 3463986
Journal Proc Natl Acad Sci U S A
Year 1986
Volume 83
Pages 7568-72
Authors Christianson DW, Lipscomb WN
Title X-ray crystallographic investigation of substrate binding to carboxypeptidase A at subzero temperature.
Related PDB 1cpa 3cpa
Related UniProtKB
[11]
Resource
Comments
Medline ID
PubMed ID 2458099
Journal Biochem J
Year 1988
Volume 251
Pages 901-5
Authors Vilanova M, Vendrell J, Cuchillo CM, Aviles FX
Title Analysis of the conformation and ligand-binding properties of the activation segment of pig procarboxypeptidase A.
Related PDB
Related UniProtKB
[12]
Resource
Comments
Medline ID
PubMed ID 3208711
Journal Eur Biophys J
Year 1988
Volume 16
Pages 95-100
Authors Kerfelec B, Chapus C, Vachette P
Title Morphology of the procarboxypeptidase A-S6 complex. A solution X-ray scattering study.
Related PDB
Related UniProtKB
[13]
Resource
Comments
Medline ID
PubMed ID
Journal Acc Chem Res
Year 1989
Volume 22
Pages 62-69
Authors Christianson DW, Lipscomb WN
Title Carboxypeptidase A
Related PDB
Related UniProtKB
[14]
Resource
Comments
Medline ID
PubMed ID 2920728
Journal Eur J Biochem
Year 1989
Volume 179
Pages 609-16
Authors Pascual R, Burgos FJ, Salva M, Soriano F, Mendez E, Aviles FX
Title Purification and properties of five different forms of human procarboxypeptidases.
Related PDB
Related UniProtKB
[15]
Resource
Comments
Medline ID
PubMed ID 2568989
Journal J Biol Chem
Year 1989
Volume 264
Pages 12849-53
Authors Christianson DW, Mangani S, Shoham G, Lipscomb WN
Title Binding of D-phenylalanine and D-tyrosine to carboxypeptidase A.
Related PDB
Related UniProtKB
[16]
Resource
Comments
Medline ID
PubMed ID 2327981
Journal Biochem J
Year 1990
Volume 267
Pages 213-20
Authors Vendrell J, Aviles FX, Vilanova M, Turner CH, Crane-Robinson C
Title 1H-n.m.r. studies of the isolated activation segment from pig procarboxypeptidase A.
Related PDB
Related UniProtKB
[17]
Resource
Comments X-ray Diffraction
Medline ID
PubMed ID 2386784
Journal Biochemistry
Year 1990
Volume 29
Pages 5546-55
Authors Kim H, Lipscomb WN
Title Crystal structure of the complex of carboxypeptidase A with a strongly bound phosphonate in a new crystalline form: comparison with structures of other complexes.
Related PDB 6cpa
Related UniProtKB
[18]
Resource
Comments
Medline ID
PubMed ID 2243116
Journal J Biol Chem
Year 1990
Volume 265
Pages 20692-8
Authors Phillips MA, Fletterick R, Rutter WJ
Title Arginine 127 stabilizes the transition state in carboxypeptidase.
Related PDB
Related UniProtKB
[19]
Resource
Comments
Medline ID
PubMed ID 2324107
Journal J Biol Chem
Year 1990
Volume 265
Pages 6949-53
Authors Vendrell J, Cuchillo CM, Aviles FX
Title The tryptic activation pathway of monomeric procarboxypeptidase A.
Related PDB
Related UniProtKB
[20]
Resource
Comments
Medline ID
PubMed ID 2104979
Journal Proc Natl Acad Sci U S A
Year 1990
Volume 87
Pages 220-4
Authors Vallee BL, Auld DS
Title Active-site zinc ligands and activated H2O of zinc enzymes.
Related PDB
Related UniProtKB
[21]
Resource
Comments X-ray Diffraction
Medline ID
PubMed ID 1868092
Journal Biochemistry
Year 1991
Volume 30
Pages 8171-80
Authors Kim H, Lipscomb WN
Title Comparison of the structures of three carboxypeptidase A-phosphonate complexes determined by X-ray crystallography.
Related PDB 7cpa 8cpa
Related UniProtKB
[22]
Resource
Comments
Medline ID
PubMed ID 2007591
Journal J Biol Chem
Year 1991
Volume 266
Pages 6393-400
Authors Mock WL, Zhang JZ
Title Mechanistically significant diastereoselection in the sulfoximine inhibition of carboxypeptidase A.
Related PDB
Related UniProtKB
[23]
Resource
Comments
Medline ID
PubMed ID 1515065
Journal Biol Chem Hoppe Seyler
Year 1992
Volume 373
Pages 387-92
Authors Vendrell J, Guasch A, Coll M, Villegas V, Billeter M, Wider G, Huber R, Wuthrich K, Aviles FX
Title Pancreatic procarboxypeptidases: their activation processes related to the structural features of the zymogens and activation segments.
Related PDB
Related UniProtKB
[24]
Resource
Comments
Medline ID
PubMed ID
Journal J Am Chem Soc
Year 1992
Volume 114
Pages 5295-5303
Authors Britt BM, Peticolas WL
Title Raman spectral evidence for an anhydride intermediate in the catalysis of ester hydrolysis by carboxypeptidase A
Related PDB
Related UniProtKB
[25]
Resource
Comments
Medline ID
PubMed ID
Journal J Am Chem Soc
Year 1992
Volume 114
Pages 2281-2282
Authors Yun M, Park C, Kim S, Nam D, Kim SC, Kim H
Title The x-ray crystallographic study of covalently modified carboxypeptidase A by 2-benzyl-3,4-epoxybutanoic acid, a pseudomechanism-based inactivator
Related PDB
Related UniProtKB
[26]
Resource
Comments X-ray Diffraction
Medline ID
PubMed ID 1527041
Journal J Biol Chem
Year 1992
Volume 267
Pages 19192-7
Authors Cappalonga AM, Alexander RS, Christianson DW
Title Structural comparison of sulfodiimine and sulfonamide inhibitors in their complexes with zinc enzymes.
Related PDB 1cps
Related UniProtKB
[27]
Resource
Comments X-RAY CRYSTALLOGRAPHY (2 ANGSTROMS) OF 17-419.
Medline ID
PubMed ID 1548696
Journal J Mol Biol
Year 1992
Volume 224
Pages 141-57
Authors Guasch A, Coll M, Aviles FX, Huber R
Title Three-dimensional structure of porcine pancreatic procarboxypeptidase A. A comparison of the A and B zymogens and their determinants for inhibition and activation.
Related PDB 1pca
Related UniProtKB P09954
[28]
Resource
Comments X-ray Diffraction
Medline ID
PubMed ID 1738164
Journal J Mol Biol
Year 1992
Volume 223
Pages 573-8
Authors Mangani S, Carloni P, Orioli P
Title Crystal structure of the complex between carboxypeptidase A and the biproduct analog inhibitor L-benzylsuccinate at 2.0 A resolution.
Related PDB 1cbx
Related UniProtKB
[29]
Resource
Comments
Medline ID
PubMed ID 1304353
Journal Protein Sci
Year 1992
Volume 1
Pages 517-21
Authors Phillips MA, Hedstrom L, Rutter WJ
Title Guanidine derivatives restore activity to carboxypeptidase lacking arginine-127.
Related PDB
Related UniProtKB
[30]
Resource
Comments X-ray Diffraction
Medline ID
PubMed ID 15299490
Journal Acta Crystallogr D Biol Crystallogr
Year 1993
Volume 49
Pages 534-40
Authors Teplyakov A, Wilson KS, Orioli P, Mangani S
Title High-resolution structure of the complex between carboxypeptidase A and L-phenyl lactate.
Related PDB 2ctb 2ctc
Related UniProtKB
[31]
Resource
Comments
Medline ID
PubMed ID 8424757
Journal Biochem J
Year 1993
Volume 289
Pages 185-93
Authors Mock WL, Freeman DJ, Aksamawati M
Title Fluxionate Lewis acidity of the Zn2+ ion in carboxypeptidase A.
Related PDB
Related UniProtKB
[32]
Resource
Comments
Medline ID
PubMed ID 8436102
Journal Eur J Biochem
Year 1993
Volume 211
Pages 381-9
Authors Aviles FX, Vendrell J, Guasch A, Coll M, Huber R
Title Advances in metallo-procarboxypeptidases. Emerging details on the inhibition mechanism and on the activation process.
Related PDB
Related UniProtKB
[33]
Resource
Comments
Medline ID
PubMed ID 8200353
Journal Eur J Biochem
Year 1994
Volume 222
Pages 55-63
Authors Oppezzo O, Ventura S, Bergman T, Vendrell J, Jornvall H, Aviles FX
Title Procarboxypeptidase in rat pancreas. Overall characterization and comparison of the activation processes.
Related PDB
Related UniProtKB
[34]
Resource
Comments
Medline ID
PubMed ID 8308030
Journal J Biol Chem
Year 1994
Volume 269
Pages 4587-95
Authors Mustafi D, Makinen MW
Title Catalytic conformation of carboxypeptidase A. Structure of a true enzyme reaction intermediate determined by electron nuclear double resonance.
Related PDB
Related UniProtKB
[35]
Resource
Comments X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF TERNARY COMPLEX.
Medline ID 96003618
PubMed ID 7556081
Journal EMBO J
Year 1995
Volume 14
Pages 4387-94
Authors Gomis-Ruth FX, Gomez M, Bode W, Huber R, Aviles FX
Title The three-dimensional structure of the native ternary complex of bovine pancreatic procarboxypeptidase A with proproteinase E and chymotrypsinogen C.
Related PDB 1pyt
Related UniProtKB P00730
[36]
Resource
Comments
Medline ID
PubMed ID 7607308
Journal FEBS Lett
Year 1995
Volume 367
Pages 211-3
Authors Gomis-Ruth FX, Gomez M, Ventura S, Vendrell J, Aviles FX
Title Crystallization and preliminary X-ray analysis of the ternary complex of procarboxypeptidase A from bovine pancreas.
Related PDB
Related UniProtKB
[37]
Resource
Comments
Medline ID
PubMed ID 11848831
Journal Chem Rev
Year 1996
Volume 96
Pages 2375-2434
Authors Lipscomb WN, Strater N
Title Recent Advances in Zinc Enzymology.
Related PDB
Related UniProtKB
[38]
Resource
Comments X-ray Diffraction
Medline ID
PubMed ID
Journal J Am Chem Soc
Year 1996
Volume 118
Pages 12479-12480
Authors Irina Massova, Philip Martin, Srini de Mel, Yasuhiro Tanaka, Brian Edwards, and Shahriar Mobashery
Title Crystallographic and Computational Insight on the Mechanism of Zinc-Ion-Dependent Inactivation of Carboxypeptidase A by 2-Benzyl-3-iodopropanoate
Related PDB 1bav
Related UniProtKB
[39]
Resource
Comments
Medline ID
PubMed ID 9220957
Journal Biochemistry
Year 1997
Volume 36
Pages 8710-5
Authors Asante-Appiah E, Seetharaman J, Sicheri F, Yang DS, Chan WW
Title Gem-dialkyl succinic acids: a novel class of inhibitors for carboxypeptidases.
Related PDB
Related UniProtKB
[40]
Resource
Comments
Medline ID
PubMed ID 9009226
Journal FEBS Lett
Year 1997
Volume 400
Pages 336-40
Authors Gomez-Ortiz M, Gomis-Ruth FX, Huber R, Aviles FX
Title Inhibition of carboxypeptidase A by excess zinc: analysis of the structural determinants by X-ray crystallography.
Related PDB
Related UniProtKB
[41]
Resource
Comments X-ray Diffraction
Medline ID
PubMed ID 9867434
Journal Acta Crystallogr D Biol Crystallogr
Year 1998
Volume 54
Pages 289-305
Authors Greenblatt HM, Feinberg H, Tucker PA, Shoham G
Title Carboxypeptidase A: native, zinc-removed and mercury-replaced forms.
Related PDB 1arl 1arm 1yme
Related UniProtKB
[42]
Resource
Comments X-ray Diffraction
Medline ID
PubMed ID 9843422
Journal Biochemistry
Year 1998
Volume 37
Pages 16555-64
Authors Bukrinsky JT, Bjerrum MJ, Kadziola A
Title Native carboxypeptidase A in a new crystal environment reveals a different conformation of the important tyrosine 248.
Related PDB 1cpx
Related UniProtKB
[43]
Resource
Comments
Medline ID
PubMed ID 9862201
Journal Protein Eng
Year 1998
Volume 11
Pages 841-5
Authors Chai JJ, He C, Li M, Tang L, Luo M
Title Crystal structure of carboxypeptidase A complexed with an inactivator in two crystal forms.
Related PDB
Related UniProtKB
[44]
Resource
Comments
Medline ID
PubMed ID 10493853
Journal J Mol Biol
Year 1999
Volume 292
Pages 11-7
Authors Makarova KS, Grishin NV
Title The Zn-peptidase superfamily: functional convergence after evolutionary divergence.
Related PDB
Related UniProtKB
[45]
Resource
Comments
Medline ID
PubMed ID 11076537
Journal Biochemistry
Year 2000
Volume 39
Pages 13945-52
Authors Mock WL, Cheng H
Title Principles of hydroxamate inhibition of metalloproteases: carboxypeptidase A.
Related PDB
Related UniProtKB
[46]
Resource
Comments X-ray Diffraction
Medline ID
PubMed ID 10955996
Journal Biochemistry
Year 2000
Volume 39
Pages 10082-9
Authors van Aalten DM, Chong CR, Joshua-Tor L
Title Crystal structure of carboxypeptidase A complexed with D-cysteine at 1.75 A - inhibitor-induced conformational changes.
Related PDB 1f57
Related UniProtKB
[47]
Resource
Comments
Medline ID
PubMed ID 10708864
Journal Biochim Biophys Acta
Year 2000
Volume 1477
Pages 284-98
Authors Vendrell J, Querol E, Aviles FX
Title Metallocarboxypeptidases and their protein inhibitors. Structure, function and biomedical properties.
Related PDB
Related UniProtKB
[48]
Resource
Comments
Medline ID
PubMed ID 10819170
Journal Bioorg Med Chem
Year 2000
Volume 8
Pages 815-23
Authors Lee M, Kim DH
Title Hippuryl-alpha-methylphenylalanine and hippuryl-alpha-methylphenyllactic acid as substrates for carboxypeptidase A. Syntheses, kinetic evaluation and mechanistic implication.
Related PDB
Related UniProtKB
[49]
Resource
Comments
Medline ID
PubMed ID 11513597
Journal Biochemistry
Year 2001
Volume 40
Pages 10197-203
Authors Cho JH, Kim DH, Lee KJ, Kim DH, Choi KY
Title The role of Tyr248 probed by mutant bovine carboxypeptidase A: insight into the catalytic mechanism of carboxypeptidase A.
Related PDB
Related UniProtKB
[50]
Resource
Comments
Medline ID
PubMed ID 11249116
Journal Bioorg Med Chem
Year 2001
Volume 9
Pages 237-43
Authors Park JD, Lee KJ, Kim DH
Title A new inhibitor design strategy for carboxypeptidase A as exemplified by N-(2-chloroethyl)-N-methylphenylalanine.
Related PDB
Related UniProtKB
[51]
Resource
Comments
Medline ID
PubMed ID 11743734
Journal J Mol Biol
Year 2001
Volume 314
Pages 1191-207
Authors Wouters MA, Husain A
Title Changes in zinc ligation promote remodeling of the active site in the zinc hydrolase superfamily.
Related PDB
Related UniProtKB
[52]
Resource
Comments
Medline ID
PubMed ID 11676544
Journal J Mol Biol
Year 2001
Volume 313
Pages 629-38
Authors Estebanez-Perpina E, Bayes A, Vendrell J, Jongsma MA, Bown DP, Gatehouse JA, Huber R, Bode W, Aviles FX, Reverter D
Title Crystal structure of a novel mid-gut procarboxypeptidase from the cotton pest Helicoverpa armigera.
Related PDB 1jqg
Related UniProtKB
[53]
Resource
Comments X-ray Diffraction
Medline ID
PubMed ID 11937361
Journal Bioorg Med Chem
Year 2002
Volume 10
Pages 2015-22
Authors Cho JH, Kim DH, Chung SJ, Ha NC, Oh BH, Yong Choi K
Title Insight into the stereochemistry in the inhibition of carboxypeptidase A with N-(hydroxyaminocarbonyl)phenylalanine: binding modes of an enantiomeric pair of the inhibitor to carboxypeptidase A.
Related PDB 1hdq 1hdu 1hee
Related UniProtKB
[54]
Resource
Comments
Medline ID
PubMed ID 11836098
Journal Bioorg Med Chem
Year 2002
Volume 10
Pages 913-22
Authors Lee M, Kim DH
Title Syntheses and kinetic evaluation of racemic and optically active 2-benzyl-2-methyl-3,4-epoxybutanoic acids as irreversible inactivators for carboxypeptidase A.
Related PDB
Related UniProtKB
[55]
Resource
Comments X-ray Diffraction
Medline ID
PubMed ID 11941507
Journal J Biol Inorg Chem
Year 2002
Volume 7
Pages 490-9
Authors Jensen F, Bukrinsky T, Bjerrum J, Larsen S
Title Three high-resolution crystal structures of cadmium-substituted carboxypeptidase A provide insight into the enzymatic function.
Related PDB 1ee3 1ell 1elm
Related UniProtKB
[56]
Resource
Comments X-ray Diffraction
Medline ID
PubMed ID 12431056
Journal J Med Chem
Year 2002
Volume 45
Pages 5295-302
Authors Park JD, Kim DH, Kim SJ, Woo JR, Ryu SE
Title Sulfamide-based inhibitors for carboxypeptidase A. Novel type transition state analogue inhibitors for zinc proteases.
Related PDB 1iy7
Related UniProtKB
[57]
Resource
Comments X-ray Diffraction
Medline ID
PubMed ID 12554943
Journal Acta Crystallogr D Biol Crystallogr
Year 2003
Volume 59
Pages 323-33
Authors Kilshtain-Vardi A, Glick M, Greenblatt HM, Goldblum A, Shoham G
Title Refined structure of bovine carboxypeptidase A at 1.25 A resolution.
Related PDB 1m4l
Related UniProtKB
[58]
Resource
Comments
Medline ID
PubMed ID 15080932
Journal Bioorg Med Chem
Year 2004
Volume 12
Pages 2349-56
Authors Park JD, Kim DH
Title Sulfamide derivatives as transition state analogue inhibitors for carboxypeptidase A.
Related PDB
Related UniProtKB
[59]
Resource
Comments
Medline ID
PubMed ID 15198587
Journal J Am Chem Soc
Year 2004
Volume 126
Pages 7452-3
Authors Liu JQ, Wulff G
Title Functional mimicry of the active site of carboxypeptidase a by a molecular imprinting strategy: cooperativity of an amidinium and a copper ion in a transition-state imprinted cavity giving rise to high catalytic activity.
Related PDB
Related UniProtKB
[60]
Resource
Comments X-ray Diffraction
Medline ID
PubMed ID 15961103
Journal J Mol Biol
Year 2005
Volume 350
Pages 489-98
Authors Arolas JL, Popowicz GM, Lorenzo J, Sommerhoff CP, Huber R, Aviles FX, Holak TA
Title The three-dimensional structures of tick carboxypeptidase inhibitor in complex with A/B carboxypeptidases reveal a novel double-headed binding mode.
Related PDB 1zlh
Related UniProtKB
[61]
Resource
Comments
Medline ID
PubMed ID 16126224
Journal J Mol Biol
Year 2005
Volume 352
Pages 961-75
Authors Arolas JL, Popowicz GM, Bronsoms S, Aviles FX, Huber R, Holak TA, Ventura S
Title Study of a major intermediate in the oxidative folding of leech carboxypeptidase inhibitor: contribution of the fourth disulfide bond.
Related PDB 2abz
Related UniProtKB

Comments
This enzyme belongs to the peptidase family-M14.
Moreover, this enzyme is homologous to carboxypeptidase A2 (E.C. 3.4.17.15; D00193 in EzCatDB), carboxypeptidase B (E.C. 3.4.17.2; D00512), carboxypeptidase T (E.C. 3.4.17.18; S00407) with conserved catalytic residues. Thus, they might have the same catalytic mechanism.
There have been two proposed mechanisms: a nucleophilic mechanism (double-displacement mechanism forming a covalent-bonded intermediate) and a promoted-water mechanism (single-displacement mechanism) (see [13]). However, many reports, including literature [13], support the promoted-water mechanism. In the promoted-water mechanism, Glu270 acts as a general base to activate the hydrolytic water together with the zinc ion. However, the literature [22] mentioned that the C-terminal carboxylate of the substrate peptid could also play such a role.
According to the literature [13], [17], [18], [21], [32], [37], [39], [51], [52], and [55], the catalytic reaction proceeds as follows:
(1) Glu270 acts as a general base to activate the hydrolytic water, along with the Zinc ion bound to His69/Glu72/His196.
(2) The activated water makes a nucleophilic attack on the target carbonyl carbon, whilst Arg127 is hydrogen bonded to the carbonyl oxygen, facilitating the formation of the tetrahedral (or gem-diolate) transition-state.
(3) The transition-state is stabilized by both Zinc ion and Arg127, along with the mainchain carbonyl of Ser197 and the sidechain oxygen of Glu270.
(4) Glu270 acts as a general acid to protonate the leaving amine group, completing the hydrolysis.

Created Updated
2005-10-26 2018-04-23