EzCatDB: S00450
Related links:    PDB-formatted query search system Fasta-formatted query search system Fasta-formatted query search system

DB codeS00450
RLCP classification1.13.30000.44 : Hydrolysis
CATH domainDomain 13.90.70.10 : Cathepsin B; Chain ACatalytic domain
E.C.3.4.22.30

CATH domainRelated DB codes (homologues)
3.90.70.10 : Cathepsin B; Chain AS00444,S00445,S00447,S00448,S00449,S00451,S00446,S00518

Enzyme Name
UniProtKBKEGG

P10056
Protein nameCaricaincaricain
papaya peptidase A
papaya peptidase II
papaya proteinase
papaya proteinase III
papaya proteinase 3
proteinase omega
papaya proteinase A
chymopapain S
Pp
SynonymsEC 3.4.22.30
Papaya proteinase omega
Papaya proteinase III
PPIII
Papaya peptidase A
PfamPF08246 (Inhibitor_I29)
PF00112 (Peptidase_C1)
[Graphical view]


UniProtKB:Accession NumberP10056
Entry namePAPA3_CARPA
ActivityHydrolysis of proteins with broad specificity for peptide bonds, similar to those of papain and chymopapain.
SubunitMonomer.
Subcellular location
Cofactor

Compound table: links to PDB-related databases & PoSSuM

SubstratesProductsintermediates
KEGG-idC00017C00012C00001C00017C00012I00153I00154I00155
CompoundProteinPeptideH2OProteinPeptidePeptidyl-Cys-tetrahedral-intermediate (with previous peptide)Acyl-enzyme(Peptidyl-Cys-acyl group)Peptidyl-Cys-tetrahedral-intermediate
Typepeptide/proteinpeptide/proteinH2Opeptide/proteinpeptide/protein


ChEBI

15377





PubChem

962
22247451





                
1megAUnboundUnbound UnboundUnboundUnboundUnboundIntermediate-analogue:E64
1ppoAUnboundUnbound UnboundUnboundUnboundUnboundUnbound
1pciAUnboundUnbound UnboundUnboundUnboundUnboundUnbound
1pciBUnboundUnbound UnboundUnboundUnboundUnboundUnbound
1pciCUnboundUnbound UnboundUnboundUnboundUnboundUnbound

Active-site residues
resource
Swiss-prot;P10056, PDB data & papers
pdbCatalytic residuesMain-chain involved in catalysiscomment
           
1megAGLN 19;CYS 25;HIS 159;ASN 179
CYS 25
mutant D158E
1ppoAGLN 19;CYS 25;HIS 159;ASN 179
CYS 25
 
1pciAGLN 19;CYS 25;       ;ASN 179
CYS 25
mutant H159G
1pciBGLN 19;CYS 25;       ;ASN 179
CYS 25
mutant H159G
1pciCGLN 19;CYS 25;       ;ASN 179
CYS 25
mutant H159G

References for Catalytic Mechanism
ReferencesSectionsNo. of steps in catalysis
[2]p.209
[3]p.1274-1276
[4]p.14770-14771l

references
[1]
JournalActa Crystallogr B
Year1991
Volume47
Pages766-771
AuthorsPickersgill RW, Rizkallah P, Harris GW, Goodenough PW
TitleDetermination of the structure of papaya protease omega.
Related PDB1ppo
[2]
PubMed ID8103322
JournalBiochem J
Year1993
Volume294
Pages201-10
AuthorsMellor GW, Patel M, Thomas EW, Brocklehurst K
TitleClarification of the pH-dependent kinetic behaviour of papain by using reactivity probes and analysis of alkylation and catalysed acylation reactions in terms of multihydronic state models: implications for electrostatics calculations and interpretation of the consequences of site-specific mutations such as Asp-158-Asn and Asp-158-Glu.
[3]
PubMed ID7855143
JournalProtein Eng
Year1994
Volume7
Pages1267-76
AuthorsTaylor MA, Baker KC, Connerton IF, Cummings NJ, Harris GW, Henderson IM, Jones ST, Pickersgill RW, Sumner IG, Warwicker J, et al
TitleAn unequivocal example of cysteine proteinase activity affected by multiple electrostatic interactions.
[4]
Commentscatalysis (rapid kinetic studies), X-ray crystallography
PubMed ID8942638
JournalBiochemistry
Year1996
Volume35
Pages14763-72
AuthorsKaterelos NA, Goodenough PW
TitleRapid kinetic studies and structural determination of a cysteine proteinase mutant imply that residue 158 in caricain has a major effect upon the ability of the active site histidine to protonate a dipyridyl probe.
Related PDB1meg
[5]
CommentsX-ray crystallography (2.0 Angstroms)
Medline ID96354872
PubMed ID8769310
JournalFEBS Lett
Year1996
Volume392
Pages35-9
AuthorsKaterelos NA, Taylor MA, Scott M, Goodenough PW, Pickersgill RW
TitleCrystal structure of a caricain D158E mutant in complex with E-64.
Related UniProtKBP10056
[6]
CommentsX-ray crystallography (3.2 Angstroms)
Medline ID97094976
PubMed ID8939744
JournalStructure
Year1996
Volume4
Pages1193-203
AuthorsGroves MR, Taylor MA, Scott M, Cummings NJ, Pickersgill RW, Jenkins JA
TitleThe prosequence of procaricain forms an alpha-helical domain that prevents access to the substrate-binding cleft.
Related PDB1pci
Related UniProtKBP10056

comments
This enzyme belongs to the peptidase family-C1.
The paper [4] mentioned that cysteine ionization alone is not sufficient to support the catalysis. The paper [2] conculded that the formation of (Cys25)S-/(His159)ImH+ ion-pair state of papain is characterized by pKa value close to 3.4. Formation of the ion-pair state of the enzyme (pKa around 3.4) appears to be sufficient for the full development of nucleophilic reactivity of the thiolate anion component of the ion-pair in the reactions.
According to the paper [3], although there are various states of ionizations for Cys25 and His159, the essential thiolate-imidazolium ion pair of cysteine proteinases must be in the form S-_ImH+ for catalytic activity to be exhibited. A negative charge at Asp158 enhances catalytic competence over and above that produced by the Cys-His ion pair alone. Thus, Asp158 plays a role as pKa modulator.
On the other hand, considering the tertiary structure of this enzyme, Asp158 does not interact with His159 directly. From a structural viewpoint, Asn179 is more likely to be the modulator for His159, as its homologous enzymes (see S00444, S00445, S00447 in EzCatDB).

createdupdated
2002-07-012012-10-23


Copyright: Nozomi Nagano, JST & CBRC-AIST
Funded by PRESTO/Japan Science and Technology Corporation (JST) (December 2001 - November 2004)
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 - )
© Biotechnology Research Institute for Drug Discovery, AIST, 2015-2016 All Rights Reserved.
© Computational Biology Research Center, AIST, 2004-2016 All Rights Reserved.