DB code: D00193

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. 3.4.17.15
CSA
M-CSA
MACiE

CATH domain Related DB codes (homologues)
3.30.70.340 : Alpha-Beta Plaits D00512 D00467
3.40.630.10 : Aminopeptidase D00512 S00406 S00407 D00192 D00467

Uniprot Enzyme Name
UniprotKB Protein name Synonyms RefSeq MEROPS Pfam
P48052 Carboxypeptidase A2
EC 3.4.17.15
NP_001860.2 (Protein)
NM_001869.2 (DNA/RNA sequence)
M14.002 (Metallo)
PF00246 (Peptidase_M14)
PF02244 (Propep_M14)
[Graphical View]

KEGG enzyme name
carboxypeptidase A2
CPA2

UniprotKB: Accession Number Entry name Activity Subunit Subcellular location Cofactor
P48052 CBPA2_HUMAN Similar to that of carboxypeptidase A (EC 3.4.17.1), but with a preference for bulkier C-terminal residues. Secreted. 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 C00151 C00012
E.C.
Compound Zinc Protein Peptide H2O L-Amino acid Peptide
Type heavy metal peptide/protein peptide/protein H2O amino acids peptide/protein
ChEBI 29105
29105
15377
15377
PubChem 32051
32051
22247451
962
22247451
962
1o6xA Unbound Unbound Unbound Unbound Unbound
1ayeA01 Unbound Unbound Unbound Unbound Unbound
1ayeA02 Bound:_ZN Unbound Unbound Unbound Unbound
1dtdA Bound:_ZN Unbound Unbound Bound:GLU_300 Bound:VAL_66(chainB)

Reference for Active-site residues
resource references E.C.
Swiss-prot;P48052 & literature [7], [18]

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
1o6xA
1ayeA01
1ayeA02 ARG 127;GLU 270 HIS 69;GLU 72;HIS 196(Zinc binding) SER 197
1dtdA ARG 482;GLU 626 HIS 424;GLU 427;HIS 552(Zinc binding) SER 553

References for Catalytic Mechanism
References Sections No. of steps in catalysis
[6]
p.6656
[7]
[18]
p.324-326

References
[1]
Resource
Comments
Medline ID
PubMed ID 3182871
Journal J Biol Chem
Year 1988
Volume 263
Pages 17828-36
Authors Gardell SJ, Craik CS, Clauser E, Goldsmith EJ, Stewart CB, Graf M, Rutter WJ
Title A novel rat carboxypeptidase, CPA2: characterization, molecular cloning, and evolutionary implications on substrate specificity in the carboxypeptidase gene family.
Related PDB
Related UniProtKB
[2]
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
[3]
Resource
Comments
Medline ID
PubMed ID 1761558
Journal J Biol Chem
Year 1991
Volume 266
Pages 24606-12
Authors Faming Z, Kobe B, Stewart CB, Rutter WJ, Goldsmith EJ
Title Structural evolution of an enzyme specificity. The structure of rat carboxypeptidase A2 at 1.9-A resolution.
Related PDB
Related UniProtKB
[4]
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
[5]
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
[6]
Resource
Comments
Medline ID
PubMed ID 7896805
Journal J Biol Chem
Year 1995
Volume 270
Pages 6651-7
Authors Catasus L, Vendrell J, Aviles FX, Carreira S, Puigserver A, Billeter M
Title The sequence and conformation of human pancreatic procarboxypeptidase A2. cDNA cloning, sequence analysis, and three-dimensional model.
Related PDB
Related UniProtKB
[7]
Resource
Comments X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS).
Medline ID 98046021
PubMed ID 9384570
Journal EMBO J
Year 1997
Volume 16
Pages 6906-13
Authors Garcia-Saez I, Reverter D, Vendrell J, Aviles FX, Coll M
Title The three-dimensional structure of human procarboxypeptidase A2. Deciphering the basis of the inhibition, activation and intrinsic activity of the zymogen.
Related PDB 1aye
Related UniProtKB P48052
[8]
Resource
Comments X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS).
Medline ID 98111000
PubMed ID 9450539
Journal FEBS Lett
Year 1997
Volume 420
Pages 7-10
Authors Reverter D, Garcia-Saez I, Catasus L, Vendrell J, Coll M, Aviles FX
Title Characterisation and preliminary X-ray diffraction analysis of human pancreatic procarboxypeptidase A2.
Related PDB
Related UniProtKB P48052
[9]
Resource
Comments
Medline ID
PubMed ID 9524066
Journal Biol Chem
Year 1998
Volume 379
Pages 149-55
Authors Aloy P, Catasus L, Villegas V, Reverter D, Vendrell J, Aviles FX
Title Comparative analysis of the sequences and three-dimensional models of human procarboxypeptidases A1, A2 and B.
Related PDB
Related UniProtKB
[10]
Resource
Comments
Medline ID
PubMed ID 9452479
Journal J Biol Chem
Year 1998
Volume 273
Pages 3535-41
Authors Reverter D, Ventura S, Villegas V, Vendrell J, Aviles FX
Title Overexpression of human procarboxypeptidase A2 in Pichia pastoris and detailed characterization of its activation pathway.
Related PDB
Related UniProtKB
[11]
Resource
Comments
Medline ID
PubMed ID 9799641
Journal J Mol Biol
Year 1998
Volume 283
Pages 1027-36
Authors Villegas V, Martinez JC, Aviles FX, Serrano L
Title Structure of the transition state in the folding process of human procarboxypeptidase A2 activation domain.
Related PDB
Related UniProtKB
[12]
Resource
Comments
Medline ID
PubMed ID 10542090
Journal Nat Struct Biol
Year 1999
Volume 6
Pages 1005-9
Authors Chiti F, Taddei N, White PM, Bucciantini M, Magherini F, Stefani M, Dobson CM
Title Mutational analysis of acylphosphatase suggests the importance of topology and contact order in protein folding.
Related PDB
Related UniProtKB
[13]
Resource
Comments
Medline ID
PubMed ID 10201391
Journal Nat Struct Biol
Year 1999
Volume 6
Pages 304-7
Authors Ionescu RM, Matthews CR
Title Folding under the influence.
Related PDB
Related UniProtKB
[14]
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
[15]
Resource
Comments
Medline ID
PubMed ID 10998048
Journal Eur J Biochem
Year 2000
Volume 267
Pages 5891-9
Authors Fernandez AM, Villegas V, Martinez JC, Van Nuland NA, Conejero-Lara F, Aviles FX, Serrano L, Filimonov VV, Mateo PL
Title Thermodynamic analysis of helix-engineered forms of the activation domain of human procarboxypeptidase A2.
Related PDB
Related UniProtKB
[16]
Resource
Comments
Medline ID
PubMed ID 10781799
Journal FEBS Lett
Year 2000
Volume 472
Pages 27-33
Authors Villanueva J, Canals F, Villegas V, Querol E, Aviles FX
Title Hydrogen exchange monitored by MALDI-TOF mass spectrometry for rapid characterization of the stability and conformation of proteins.
Related PDB
Related UniProtKB
[17]
Resource
Comments
Medline ID
PubMed ID 10702927
Journal J Comput Aided Mol Des
Year 2000
Volume 14
Pages 83-92
Authors Aloy P, Mas JM, Marti-Renom MA, Querol E, Aviles FX, Oliva B
Title Refinement of modelled structures by knowledge-based energy profiles and secondary structure prediction: application to the human procarboxypeptidase A2.
Related PDB
Related UniProtKB
[18]
Resource
Comments X-ray crystallography
Medline ID
PubMed ID 10742178
Journal Nat Struct Biol
Year 2000
Volume 7
Pages 322-8
Authors Reverter D, Fernandez-Catalan C, Baumgartner R, Pfander R, Huber R, Bode W, Vendrell J, Holak TA, Aviles FX
Title Structure of a novel leech carboxypeptidase inhibitor determined free in solution and in complex with human carboxypeptidase A2.
Related PDB 1dtd
Related UniProtKB
[19]
Resource
Comments
Medline ID
PubMed ID 11045616
Journal Protein Sci
Year 2000
Volume 9
Pages 1700-8
Authors Villegas V, Zurdo J, Filimonov VV, Aviles FX, Dobson CM, Serrano L
Title Protein engineering as a strategy to avoid formation of amyloid fibrils.
Related PDB
Related UniProtKB
[20]
Resource
Comments
Medline ID
PubMed ID 12271440
Journal J Mass Spectrom
Year 2002
Volume 37
Pages 974-84
Authors Villanueva J, Villegas V, Querol E, Aviles FX, Serrano L
Title Protein secondary structure and stability determined by combining exoproteolysis and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry.
Related PDB
Related UniProtKB
[21]
Resource
Comments NMR, 20 Structures
Medline ID
PubMed ID 12538893
Journal Protein Sci
Year 2003
Volume 12
Pages 296-305
Authors Jimenez MA, Villegas V, Santoro J, Serrano L, Vendrell J, Aviles FX, Rico M
Title NMR solution structure of the activation domain of human procarboxypeptidase A2.
Related PDB 1o6x
Related UniProtKB

Comments
This enzyme belongs to the peptidase family-M14.
Moreover, this enzyme is homologous to carboxypeptidase A (E.C. 3.4.17.1; D00467 in EzCatDB), carboxypeptidase B (E.C. 3.4.17.2; D00512) and carboxypeptidase T (E.C. 3.4.17.18; S00407 in EzCatDB) with conserved catalytic residues. Thus, they might have the same catalytic mechanism.
1o6x and the N-terminal region of 1aye (of PDB) correspond to the structure of activation peptide.

Created Updated
2005-10-21 2009-02-26