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 15377
PubChem			22247451 962 22247451 962

1gecE	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	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.

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