DB code: S00449

RLCP classification 1.13.30000.44 : Hydrolysis
CATH domain 3.90.70.10 : Cathepsin B; Chain A Catalytic domain
E.C. 3.4.22.25
CSA
M-CSA
MACiE

CATH domain Related DB codes (homologues)
3.90.70.10 : Cathepsin B; Chain A S00444 S00445 S00447 S00448 S00450 S00451 S00446 S00518

Uniprot Enzyme Name
UniprotKB Protein name Synonyms MEROPS Pfam
P05994 Papaya proteinase 4
EC 3.4.22.25
Papaya proteinase IV
PPIV
Papaya peptidase B
Glycyl endopeptidase
I29.003 ()
PF08246 (Inhibitor_I29)
PF00112 (Peptidase_C1)
[Graphical View]

KEGG enzyme name
glycyl endopeptidase
papaya peptidase B
papaya proteinase IV
glycine-specific proteinase
chymopapain
Papaya proteinase 4
PPIV
chymopapain M

UniprotKB: Accession Number Entry name Activity Subunit Subcellular location Cofactor
P05994 PAPA4_CARPA Preferential cleavage: Gly-|-Xaa, in proteins and in small molecule substrates.

KEGG Pathways
Map code Pathways E.C.

Compound table
Substrates Products Intermediates
KEGG-id C00017 C00012 C00001 C00017 C00012 I00153 I00154 I00155
E.C.
Compound Protein Peptide H2O Protein Peptide Peptidyl-Cys-tetrahedral-intermediate (with previous peptide) Acyl-enzyme(Peptidyl-Cys-acyl group) Peptidyl-Cys-tetrahedral-intermediate
Type peptide/protein peptide/protein H2O peptide/protein peptide/protein
ChEBI 15377
PubChem 962
22247451
1gecE Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Intermediate-analogue:PHQ-LEU-VAL-GLY-0HQ (chain I) Unbound

Reference for Active-site residues
resource references E.C.
Swiss-prot;P05994

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
1gecE Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain GLN 19;CYS 25;HIS 159;ASN 179 CYS 25

References for Catalytic Mechanism
References Sections No. of steps in catalysis
[1]
p.814-818

References
[1]
Resource
Comments
Medline ID
PubMed ID 8010964
Journal Biochem J
Year 1994
Volume 300
Pages 805-20
Authors Thomas MP, Topham CM, Kowlessur D, Mellor GW, Thomas EW, Whitford D, Brocklehurst K
Title Structure of chymopapain M the late-eluted chymopapain deduced by comparative modelling techniques and active-centre characteristics determined by pH-dependent kinetics of catalysis and reactions with time-dependent inhibitors: the Cys-25/His-159 ion-pair is insufficient for catalytic competence in both chymopapain M and papain.
Related PDB
Related UniProtKB
[2]
Resource
Comments X-ray crystallography (2.1 Angstroms)
Medline ID
PubMed ID 7548082
Journal Biochemistry
Year 1995
Volume 34
Pages 13190-5
Authors O'Hara BP, Hemmings AM, Buttle DJ, Pearl LH
Title Crystal structure of glycyl endopeptidase from Carica papaya: a cysteine endopeptidase of unusual substrate specificity.
Related PDB 1gec
Related UniProtKB P05994
[3]
Resource
Comments
Medline ID
PubMed ID 8862553
Journal Protein Eng
Year 1996
Volume 9
Pages 525-9
Authors Baker KC, Taylor MA, Cummings NJ, Tunon MA, Worboys KA, Connerton IF
Title Autocatalytic processing of pro-papaya proteinase IV is prevented by crowding of the active-site cleft.
Related PDB
Related UniProtKB

Comments
This enzyme belongs to the peptidase family-C1.
According to the paper [1], the catalytic mechanism of this enzyme could be analogous to those in papain and other cysteine proteinases. Moreover, the Cys25/His159 ion-pair is insufficient for catalytc competence in these enzymes [1].
Considering the structural similarities to other homologous peptidases, the sidechain of Gln19 might form an oxyanion hole, together with the mainchain amide of Cys25.

Created Updated
2002-07-01 2012-10-23