EzCatDB: D00193
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DB codeD00193
RLCP classification1.13.11110.262 : Hydrolysis
CATH domainDomain 13.30.70.340 : Alpha-Beta Plaits
Domain 23.40.630.10 : AminopeptidaseCatalytic domain
E.C.3.4.17.15

CATH domainRelated DB codes (homologues)
3.30.70.340 : Alpha-Beta PlaitsD00512,D00467
3.40.630.10 : AminopeptidaseD00512,S00406,S00407,D00192,D00467

Enzyme Name
UniProtKBKEGG

P48052
Protein nameCarboxypeptidase A2carboxypeptidase A2
CPA2
SynonymsEC 3.4.17.15
RefSeqNP_001860.2 (Protein)
NM_001869.2 (DNA/RNA sequence)
MEROPSM14.002 (Metallo)
PfamPF00246 (Peptidase_M14)
PF02244 (Propep_M14)
[Graphical view]


UniProtKB:Accession NumberP48052
Entry nameCBPA2_HUMAN
ActivitySimilar to that of carboxypeptidase A (EC 3.4.17.1), but with a preference for bulkier C-terminal residues.
Subunit
Subcellular locationSecreted.
CofactorBinds 1 zinc ion per subunit.

Compound table: links to PDB-related databases & PoSSuM

CofactorsSubstratesProducts
KEGG-idC00038C00017C00012C00001C00151C00012
CompoundZincProteinPeptideH2OL-Amino acidPeptide
Typeheavy metalpeptide/proteinpeptide/proteinH2Oamino acidspeptide/protein
ChEBI29105


15377


PubChem32051


962
22247451


              
1o6xAUnboundUnboundUnbound UnboundUnbound
1ayeA01UnboundUnboundUnbound UnboundUnbound
1ayeA02Bound:_ZNUnboundUnbound UnboundUnbound
1dtdABound:_ZNUnboundUnbound Bound:GLU 300Bound:VAL 66(chainB)

Active-site residues
resource
Swiss-prot;P48052 & literature [7], [18]
pdbCatalytic residuesCofactor-binding residuesMain-chain involved in catalysis
           
1o6xA 
 
 
1ayeA01 
 
 
1ayeA02ARG 127;GLU 270
HIS  69;GLU  72;HIS 196(Zinc binding)
SER 197
1dtdAARG 482;GLU 626
HIS 424;GLU 427;HIS 552(Zinc binding)
SER 553

References for Catalytic Mechanism
ReferencesSectionsNo. of steps in catalysis
[6]p.6656
[7]

[18]p.324-326

references
[1]
PubMed ID3182871
JournalJ Biol Chem
Year1988
Volume263
Pages17828-36
AuthorsGardell SJ, Craik CS, Clauser E, Goldsmith EJ, Stewart CB, Graf M, Rutter WJ
TitleA novel rat carboxypeptidase, CPA2: characterization, molecular cloning, and evolutionary implications on substrate specificity in the carboxypeptidase gene family.
[2]
PubMed ID2920728
JournalEur J Biochem
Year1989
Volume179
Pages609-16
AuthorsPascual R, Burgos FJ, Salva M, Soriano F, Mendez E, Aviles FX
TitlePurification and properties of five different forms of human procarboxypeptidases.
[3]
PubMed ID1761558
JournalJ Biol Chem
Year1991
Volume266
Pages24606-12
AuthorsFaming Z, Kobe B, Stewart CB, Rutter WJ, Goldsmith EJ
TitleStructural evolution of an enzyme specificity. The structure of rat carboxypeptidase A2 at 1.9-A resolution.
[4]
PubMed ID8436102
JournalEur J Biochem
Year1993
Volume211
Pages381-9
AuthorsAviles FX, Vendrell J, Guasch A, Coll M, Huber R
TitleAdvances in metallo-procarboxypeptidases. Emerging details on the inhibition mechanism and on the activation process.
[5]
PubMed ID8200353
JournalEur J Biochem
Year1994
Volume222
Pages55-63
AuthorsOppezzo O, Ventura S, Bergman T, Vendrell J, Jornvall H, Aviles FX
TitleProcarboxypeptidase in rat pancreas. Overall characterization and comparison of the activation processes.
[6]
PubMed ID7896805
JournalJ Biol Chem
Year1995
Volume270
Pages6651-7
AuthorsCatasus L, Vendrell J, Aviles FX, Carreira S, Puigserver A, Billeter M
TitleThe sequence and conformation of human pancreatic procarboxypeptidase A2. cDNA cloning, sequence analysis, and three-dimensional model.
[7]
CommentsX-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS).
Medline ID98046021
PubMed ID9384570
JournalEMBO J
Year1997
Volume16
Pages6906-13
AuthorsGarcia-Saez I, Reverter D, Vendrell J, Aviles FX, Coll M
TitleThe three-dimensional structure of human procarboxypeptidase A2. Deciphering the basis of the inhibition, activation and intrinsic activity of the zymogen.
Related PDB1aye
Related UniProtKBP48052
[8]
CommentsX-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS).
Medline ID98111000
PubMed ID9450539
JournalFEBS Lett
Year1997
Volume420
Pages7-10
AuthorsReverter D, Garcia-Saez I, Catasus L, Vendrell J, Coll M, Aviles FX
TitleCharacterisation and preliminary X-ray diffraction analysis of human pancreatic procarboxypeptidase A2.
Related UniProtKBP48052
[9]
PubMed ID9524066
JournalBiol Chem
Year1998
Volume379
Pages149-55
AuthorsAloy P, Catasus L, Villegas V, Reverter D, Vendrell J, Aviles FX
TitleComparative analysis of the sequences and three-dimensional models of human procarboxypeptidases A1, A2 and B.
[10]
PubMed ID9452479
JournalJ Biol Chem
Year1998
Volume273
Pages3535-41
AuthorsReverter D, Ventura S, Villegas V, Vendrell J, Aviles FX
TitleOverexpression of human procarboxypeptidase A2 in Pichia pastoris and detailed characterization of its activation pathway.
[11]
PubMed ID9799641
JournalJ Mol Biol
Year1998
Volume283
Pages1027-36
AuthorsVillegas V, Martinez JC, Aviles FX, Serrano L
TitleStructure of the transition state in the folding process of human procarboxypeptidase A2 activation domain.
[12]
PubMed ID10542090
JournalNat Struct Biol
Year1999
Volume6
Pages1005-9
AuthorsChiti F, Taddei N, White PM, Bucciantini M, Magherini F, Stefani M, Dobson CM
TitleMutational analysis of acylphosphatase suggests the importance of topology and contact order in protein folding.
[13]
PubMed ID10201391
JournalNat Struct Biol
Year1999
Volume6
Pages304-7
AuthorsIonescu RM, Matthews CR
TitleFolding under the influence.
[14]
PubMed ID10708864
JournalBiochim Biophys Acta
Year2000
Volume1477
Pages284-98
AuthorsVendrell J, Querol E, Aviles FX
TitleMetallocarboxypeptidases and their protein inhibitors. Structure, function and biomedical properties.
[15]
PubMed ID10998048
JournalEur J Biochem
Year2000
Volume267
Pages5891-9
AuthorsFernandez AM, Villegas V, Martinez JC, Van Nuland NA, Conejero-Lara F, Aviles FX, Serrano L, Filimonov VV, Mateo PL
TitleThermodynamic analysis of helix-engineered forms of the activation domain of human procarboxypeptidase A2.
[16]
PubMed ID10781799
JournalFEBS Lett
Year2000
Volume472
Pages27-33
AuthorsVillanueva J, Canals F, Villegas V, Querol E, Aviles FX
TitleHydrogen exchange monitored by MALDI-TOF mass spectrometry for rapid characterization of the stability and conformation of proteins.
[17]
PubMed ID10702927
JournalJ Comput Aided Mol Des
Year2000
Volume14
Pages83-92
AuthorsAloy P, Mas JM, Marti-Renom MA, Querol E, Aviles FX, Oliva B
TitleRefinement of modelled structures by knowledge-based energy profiles and secondary structure prediction: application to the human procarboxypeptidase A2.
[18]
CommentsX-ray crystallography
PubMed ID10742178
JournalNat Struct Biol
Year2000
Volume7
Pages322-8
AuthorsReverter D, Fernandez-Catalan C, Baumgartner R, Pfander R, Huber R, Bode W, Vendrell J, Holak TA, Aviles FX
TitleStructure of a novel leech carboxypeptidase inhibitor determined free in solution and in complex with human carboxypeptidase A2.
Related PDB1dtd
[19]
PubMed ID11045616
JournalProtein Sci
Year2000
Volume9
Pages1700-8
AuthorsVillegas V, Zurdo J, Filimonov VV, Aviles FX, Dobson CM, Serrano L
TitleProtein engineering as a strategy to avoid formation of amyloid fibrils.
[20]
PubMed ID12271440
JournalJ Mass Spectrom
Year2002
Volume37
Pages974-84
AuthorsVillanueva J, Villegas V, Querol E, Aviles FX, Serrano L
TitleProtein secondary structure and stability determined by combining exoproteolysis and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry.
[21]
CommentsNMR, 20 Structures
PubMed ID12538893
JournalProtein Sci
Year2003
Volume12
Pages296-305
AuthorsJimenez MA, Villegas V, Santoro J, Serrano L, Vendrell J, Aviles FX, Rico M
TitleNMR solution structure of the activation domain of human procarboxypeptidase A2.
Related PDB1o6x

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.

createdupdated
2005-10-212009-02-26


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Funded by BIRD/Japan Science and Technology Corporation (JST) (October 2007 - September 2010)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2011 - March 2012)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2012 - March 2013)
Supported by the commission for the Development of Artificial Gene Synthesis Technology for Creating Innovative Biomaterial from the Ministry of Economy, Trade and Industry (METI) (October 2012 - )
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