EzCatDB: D00437
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DB codeD00437
RLCP classification1.13.200.966 : Hydrolysis
CATH domainDomain 12.40.70.10 : Cathepsin D, subunit A; domain 1Catalytic domain
Domain 22.40.70.10 : Cathepsin D, subunit A; domain 1Catalytic domain
E.C.3.4.23.3
CSA1avf

CATH domainRelated DB codes (homologues)
2.40.70.10 : Cathepsin D, subunit A; domain 1D00471,D00436,D00438,D00439,D00440,D00441,D00442,D00443,D00444,D00423,D00445,D00484,M00206,M00166,D00231,D00529

Enzyme Name
UniProtKBKEGG

P20142
Protein nameGastricsingastricsin
pepsin C
pig parapepsin II
parapepsin II
SynonymsEC 3.4.23.3
Pepsinogen C
RefSeqNP_001159896.1 (Protein)
NM_001166424.1 (DNA/RNA sequence)
NP_002621.1 (Protein)
NM_002630.3 (DNA/RNA sequence)
MEROPSA01.003 (Aspartic)
PfamPF07966 (A1_Propeptide)
PF00026 (Asp)
[Graphical view]


UniProtKB:Accession NumberP20142
Entry namePEPC_HUMAN
ActivityMore restricted specificity than pepsin A, but shows preferential cleavage at Tyr-|-Xaa bonds. High activity on hemoglobin.
Subunit
Subcellular locationSecreted.
Cofactor

Compound table: links to PDB-related databases & PoSSuM

SubstratesProductsintermediates
KEGG-idC00017C00012C01708C00001C00017C00012I00136
CompoundProteinPeptideHemoglobinH2OProteinPeptideAmino-diol-tetrahedral intermediate
Typepeptide/proteinpeptide/proteinpeptide/proteinH2Opeptide/proteinpeptide/protein
ChEBI


15377



PubChem


962
22247451



               
1avfA01UnboundUnboundUnbound UnboundUnboundUnbound
1avfJ01UnboundUnboundUnbound UnboundUnboundUnbound
1htrB01UnboundUnboundUnbound UnboundUnboundUnbound
1avfA02UnboundUnboundUnbound UnboundUnboundUnbound
1avfJ02UnboundUnboundUnbound UnboundUnboundUnbound
1htrB02UnboundUnboundUnbound UnboundUnboundUnbound
1avfPUnboundUnboundUnbound UnboundUnboundUnbound
1avfQUnboundUnboundUnbound UnboundUnboundUnbound
1htrPUnboundUnboundUnbound UnboundUnboundUnbound

Active-site residues
resource
PDB;1htr & Swiss-prot;P20142
pdbCatalytic residues
         
1avfA01ASP  32
1avfJ01ASP  32
1htrB01ASP  32
1avfA02ASP 217
1avfJ02ASP 217
1htrB02ASP 217
1avfP 
1avfQ 
1htrP 

References for Catalytic Mechanism
ReferencesSectionsNo. of steps in catalysis
[1]Fig.3
[3]p.55-56
[12]Fig.4

references
[1]
PubMed ID339690
JournalAdv Exp Med Biol
Year1977
Volume95
Pages199-210
AuthorsMarciniszyn J Jr, Hartsuck JA, Tang J
TitlePepstatin inhibition mechanism.
[2]
PubMed ID38772
JournalBiochem J
Year1979
Volume179
Pages239-46
AuthorsAuffret CA, Ryle AP
TitleThe catalytic activity of pig pepsin C towards small synthetic substrates.
[3]
PubMed ID3546346
JournalJ Cell Biochem
Year1987
Volume33
Pages53-63
AuthorsTang J, Wong RN
TitleEvolution in the structure and function of aspartic proteases.
[4]
PubMed ID2500427
JournalJ Biochem (Tokyo)
Year1989
Volume105
Pages15-22
AuthorsKageyama T, Ichinose M, Miki K, Athauda SB, Tanji M, Takahashi K
TitleDifference of activation processes and structure of activation peptides in human pepsinogens A and progastricsin.
[5]
PubMed ID2111133
JournalBiochem J
Year1990
Volume267
Pages665-9
AuthorsBaxter A, Campbell CJ, Grinham CJ, Keane RM, Lawton BC, Pendlebury JE
TitleSubstrate and inhibitor studies with human gastric aspartic proteinases.
[6]
PubMed ID8410973
JournalJ Med Chem
Year1993
Volume36
Pages2614-20
AuthorsRao CM, Scarborough PE, Kay J, Batley B, Rapundalo S, Klutchko S, Taylor MD, Lunney EA, Humblet CC, Dunn BM
TitleSpecificity in the binding of inhibitors to the active site of human/primate aspartic proteinases: analysis of P2-P1-P1'-P2' variation.
[7]
CommentsX-RAY CRYSTALLOGRAPHY (1.62 ANGSTROMS)
Medline ID95230687
PubMed ID7714902
JournalJ Mol Biol
Year1995
Volume247
Pages466-85
AuthorsMoore SA, Sielecki AR, Chernaia MM, Tarasova NI, James MN
TitleCrystal and molecular structures of human progastricsin at 1.62 A resolution.
Related PDB1htr
Related UniProtKBP20142
[8]
CommentsX-RAY CRYSTALLOGRAPHY (2.36 ANGSTROMS)
Medline ID98069649
PubMed ID9406551
JournalNat Struct Biol
Year1997
Volume4
Pages1010-5
AuthorsKhan AR, Cherney MM, Tarasova NI, James MN
TitleStructural characterization of activation 'intermediate 2' on the pathway to human gastricsin.
Related PDB1avf
Related UniProtKBP20142
[9]
PubMed ID9561229
JournalAdv Exp Med Biol
Year1998
Volume436
Pages265-70
AuthorsKhan AR, Chernaia MM, Tarasova NI, James MN
TitleCrystallographic studies of an activation intermediate of human gastricsin.
[10]
PubMed ID9794784
JournalBiochem J
Year1998
Volume335
Pages481-90
AuthorsRichter C, Tanaka T, Yada RY
TitleMechanism of activation of the gastric aspartic proteinases: pepsinogen, progastricsin and prochymosin.
[11]
PubMed ID10500110
JournalProc Natl Acad Sci U S A
Year1999
Volume96
Pages10968-75
AuthorsKhan AR, Khazanovich-Bernstein N, Bergmann EM, James MN
TitleStructural aspects of activation pathways of aspartic protease zymogens and viral 3C protease precursors.
[12]
PubMed ID11922623
JournalBiochem Biophys Res Commun
Year2002
Volume292
Pages702-8
AuthorsChou KC, Howe WJ
TitlePrediction of the tertiary structure of the beta-secretase zymogen.

comments
This enzyme belongs to the peptidase family-A1. It has a catalytic dyad, composed of two aspartic acid residues, suggesting that it has a similar catalytic mechanism to that of pepsin (D00436 in EzCatDB).

createdupdated
2004-03-242012-06-27


Copyright: Nozomi Nagano, JST & CBRC-AIST
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Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2005 - March 2006)
Funded by Grant-in-Aid for Scientific Research (B)/Japan Society for the Promotion of Science (JSPS) (April 2005 - March 2008)
Funded by BIRD/Japan Science and Technology Corporation (JST) (September 2005 - September 2008)
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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