DB code: D00437

RLCP classification 1.13.200.966 : Hydrolysis
CATH domain 2.40.70.10 : Cathepsin D, subunit A; domain 1 Catalytic domain
2.40.70.10 : Cathepsin D, subunit A; domain 1 Catalytic domain
E.C. 3.4.23.3
CSA 1avf
M-CSA 1avf
MACiE

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

Uniprot Enzyme Name
UniprotKB Protein name Synonyms RefSeq MEROPS Pfam
P20142 Gastricsin
EC 3.4.23.3
Pepsinogen C
NP_001159896.1 (Protein)
NM_001166424.1 (DNA/RNA sequence)
NP_002621.1 (Protein)
NM_002630.3 (DNA/RNA sequence)
A01.003 (Aspartic)
PF07966 (A1_Propeptide)
PF00026 (Asp)
[Graphical View]

KEGG enzyme name
gastricsin
pepsin C
pig parapepsin II
parapepsin II

UniprotKB: Accession Number Entry name Activity Subunit Subcellular location Cofactor
P20142 PEPC_HUMAN More restricted specificity than pepsin A, but shows preferential cleavage at Tyr-|-Xaa bonds. High activity on hemoglobin. Secreted.

KEGG Pathways
Map code Pathways E.C.

Compound table
Substrates Products Intermediates
KEGG-id C00017 C00012 C01708 C00001 C00017 C00012 I00136
E.C.
Compound Protein Peptide Hemoglobin H2O Protein Peptide Amino-diol-tetrahedral intermediate
Type peptide/protein peptide/protein peptide/protein H2O peptide/protein peptide/protein
ChEBI 15377
 15377
PubChem 22247451
 962
 22247451
 962
1avfA01 Unbound Unbound Unbound Unbound Unbound Unbound
1avfJ01 Unbound Unbound Unbound Unbound Unbound Unbound
1htrB01 Unbound Unbound Unbound Unbound Unbound Unbound
1avfA02 Unbound Unbound Unbound Unbound Unbound Unbound
1avfJ02 Unbound Unbound Unbound Unbound Unbound Unbound
1htrB02 Unbound Unbound Unbound Unbound Unbound Unbound
1avfP Unbound Unbound Unbound Unbound Unbound Unbound
1avfQ Unbound Unbound Unbound Unbound Unbound Unbound
1htrP Unbound Unbound Unbound Unbound Unbound Unbound

Reference for Active-site residues
resource references E.C.
PDB;1htr & Swiss-prot;P20142

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
1avfA01 ASP 32
1avfJ01 ASP 32
1htrB01 ASP 32
1avfA02 ASP 217
1avfJ02 ASP 217
1htrB02 ASP 217
1avfP
1avfQ
1htrP

References for Catalytic Mechanism
References Sections No. of steps in catalysis
[1]
Fig.3
[3]
p.55-56
[12]
Fig.4

References
[1]
Resource
Comments
Medline ID
PubMed ID 339690
Journal Adv Exp Med Biol
Year 1977
Volume 95
Pages 199-210
Authors Marciniszyn J Jr, Hartsuck JA, Tang J
Title Pepstatin inhibition mechanism.
Related PDB
Related UniProtKB
[2]
Resource
Comments
Medline ID
PubMed ID 38772
Journal Biochem J
Year 1979
Volume 179
Pages 239-46
Authors Auffret CA, Ryle AP
Title The catalytic activity of pig pepsin C towards small synthetic substrates.
Related PDB
Related UniProtKB
[3]
Resource
Comments
Medline ID
PubMed ID 3546346
Journal J Cell Biochem
Year 1987
Volume 33
Pages 53-63
Authors Tang J, Wong RN
Title Evolution in the structure and function of aspartic proteases.
Related PDB
Related UniProtKB
[4]
Resource
Comments
Medline ID
PubMed ID 2500427
Journal J Biochem (Tokyo)
Year 1989
Volume 105
Pages 15-22
Authors Kageyama T, Ichinose M, Miki K, Athauda SB, Tanji M, Takahashi K
Title Difference of activation processes and structure of activation peptides in human pepsinogens A and progastricsin.
Related PDB
Related UniProtKB
[5]
Resource
Comments
Medline ID
PubMed ID 2111133
Journal Biochem J
Year 1990
Volume 267
Pages 665-9
Authors Baxter A, Campbell CJ, Grinham CJ, Keane RM, Lawton BC, Pendlebury JE
Title Substrate and inhibitor studies with human gastric aspartic proteinases.
Related PDB
Related UniProtKB
[6]
Resource
Comments
Medline ID
PubMed ID 8410973
Journal J Med Chem
Year 1993
Volume 36
Pages 2614-20
Authors Rao CM, Scarborough PE, Kay J, Batley B, Rapundalo S, Klutchko S, Taylor MD, Lunney EA, Humblet CC, Dunn BM
Title Specificity in the binding of inhibitors to the active site of human/primate aspartic proteinases: analysis of P2-P1-P1'-P2' variation.
Related PDB
Related UniProtKB
[7]
Resource
Comments X-RAY CRYSTALLOGRAPHY (1.62 ANGSTROMS)
Medline ID 95230687
PubMed ID 7714902
Journal J Mol Biol
Year 1995
Volume 247
Pages 466-85
Authors Moore SA, Sielecki AR, Chernaia MM, Tarasova NI, James MN
Title Crystal and molecular structures of human progastricsin at 1.62 A resolution.
Related PDB 1htr
Related UniProtKB P20142
[8]
Resource
Comments X-RAY CRYSTALLOGRAPHY (2.36 ANGSTROMS)
Medline ID 98069649
PubMed ID 9406551
Journal Nat Struct Biol
Year 1997
Volume 4
Pages 1010-5
Authors Khan AR, Cherney MM, Tarasova NI, James MN
Title Structural characterization of activation 'intermediate 2' on the pathway to human gastricsin.
Related PDB 1avf
Related UniProtKB P20142
[9]
Resource
Comments
Medline ID
PubMed ID 9561229
Journal Adv Exp Med Biol
Year 1998
Volume 436
Pages 265-70
Authors Khan AR, Chernaia MM, Tarasova NI, James MN
Title Crystallographic studies of an activation intermediate of human gastricsin.
Related PDB
Related UniProtKB
[10]
Resource
Comments
Medline ID
PubMed ID 9794784
Journal Biochem J
Year 1998
Volume 335
Pages 481-90
Authors Richter C, Tanaka T, Yada RY
Title Mechanism of activation of the gastric aspartic proteinases: pepsinogen, progastricsin and prochymosin.
Related PDB
Related UniProtKB
[11]
Resource
Comments
Medline ID
PubMed ID 10500110
Journal Proc Natl Acad Sci U S A
Year 1999
Volume 96
Pages 10968-75
Authors Khan AR, Khazanovich-Bernstein N, Bergmann EM, James MN
Title Structural aspects of activation pathways of aspartic protease zymogens and viral 3C protease precursors.
Related PDB
Related UniProtKB
[12]
Resource
Comments
Medline ID
PubMed ID 11922623
Journal Biochem Biophys Res Commun
Year 2002
Volume 292
Pages 702-8
Authors Chou KC, Howe WJ
Title Prediction of the tertiary structure of the beta-secretase zymogen.
Related PDB
Related UniProtKB

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).

Created Updated
2004-03-24 2012-06-27