EzCatDB: S00447
Related links:    PDB-formatted query search system Fasta-formatted query search system Fasta-formatted query search system

DB codeS00447
RLCP classification1.13.30000.44 : Hydrolysis
CATH domainDomain 13.90.70.10 : Cathepsin B; Chain ACatalytic domain
E.C.3.4.22.14

CATH domainRelated DB codes (homologues)
3.90.70.10 : Cathepsin B; Chain AS00444,S00445,S00448,S00449,S00450,S00451,S00446,S00518

Enzyme Name
UniProtKBKEGG

P00785
Protein nameActinidain (Actinidin) (EC 3.4.22.14)AltName: Allergen=Act c 1;actinidain
actinidin
Actinidia anionic protease
proteinase A2 of Actinidia chinensis
SynonymsNone
PfamPF08246 (Inhibitor_I29)
PF00112 (Peptidase_C1)
[Graphical view]


UniProtKB:Accession NumberP00785
Entry nameACTN_ACTCH
ActivitySpecificity close to that of papain.
Subunit
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





                
1aecAUnboundUnbound UnboundUnboundUnboundUnboundIntermediate-analogue:E64
2actAUnboundUnbound UnboundUnboundUnboundUnboundUnbound

Active-site residues
resource
Swiss-prot;P00785 & literature [2]
pdbCatalytic residuesMain-chain involved in catalysis
          
1aecAGLN 19;CYS 25;HIS 162;ASN 182
CYS 25
2actAGLN 19;CYS 25;HIS 162;ASN 182
CYS 25

References for Catalytic Mechanism
ReferencesSectionsNo. of steps in catalysis
[2]p.469-476
[3]p.5174-5175

references
[1]
CommentsX-ray crystallography (1.7 Angstroms)
PubMed IDnot found
JournalActa Crystallogr.,Sect.A
Year1980
Volume36
Pages559
AuthorsE.N.Baker,E.J.Dodson
TitleCrystallographic refinement of the structure of actinidin at 1.7 angstroms resolution by fast fourier least-*squares methods.
Related PDB2act
[2]
CommentsX-ray crystallography (1.7 Angstroms)
Medline ID81072298
PubMed ID7003158
JournalJ Mol Biol
Year1980
Volume141
Pages441-84
AuthorsBaker EN
TitleStructure of actinidin, after refinement at 1.7 A resolution.
Related UniProtKBP00785
[3]
CommentsX-ray crystallography (1.86 Angstroms)
PubMed ID1606141
JournalBiochemistry
Year1992
Volume31
Pages5172-6
AuthorsVarughese KI, Su Y, Cromwell D, Hasnain S, Xuong NH
TitleCrystal structure of an actinidin-E-64 complex.
Related PDB1aec
[4]
PubMed ID7958276
JournalBiochem Soc Trans
Year1994
Volume22
Pages214S
AuthorsPatel M, Thomas MP, Noble MA, Gul S, Thomas EW, Brocklehurst K
TitleVariation in the effects of P2-S2 binding contacts on catalytic site chemistry among members of the cysteine proteinase family.
[5]
PubMed ID9649846
JournalBiochem Soc Trans
Year1998
Volume26
PagesS171
AuthorsGul S, Pinitglang S, Thomas EW, Verma C, Brocklehurst K
TitleSensitivities of transition state geometries to P1-P2 binding in reactions of papain and actinidin.
[6]
PubMed ID9649848
JournalBiochem Soc Trans
Year1998
Volume26
PagesS173
AuthorsReid JD, Sreedharan S, Cole A, Maskell S, Bokth A, Thomas EW, Brocklehurst K
TitleDetection of a free enzyme isomerisation in actinidin catalysed hydrolysis.
[7]
PubMed ID11439083
JournalBiochem J
Year2001
Volume357
Pages343-52
AuthorsReid JD, Hussain S, Sreedharan SK, Bailey TS, Pinitglang S, Thomas EW, Verma CS, Brocklehurst K
TitleVariation in aspects of cysteine proteinase catalytic mechanism deduced by spectroscopic observation of dithioester intermediates, kinetic analysis and molecular dynamics simulations.
[8]
PubMed ID12643810
JournalBiochem J
Year2003
Volume372
Pages735-46
AuthorsHussain S, Pinitglang S, Bailey TS, Reid JD, Noble MA, Resmini M, Thomas EW, Greaves RB, Verma CS, Brocklehurst K
TitleVariation in the pH-dependent pre-steady-state and steady-state kinetic characteristics of cysteine-proteinase mechanism: evidence for electrostatic modulation of catalytic-site function by the neighbouring carboxylate anion.

comments
According to the paper [3], Cys25 seems to play a nucleophilic role, which will attack the carbonyl carbon atom to form covalent bond with the substrate. Furthermore, this paper mentioned that the catalysis might proceed in an SN2-like reaction.
Moreover, the paper [2] reported that the mainchain amide of Cys25 and the sidechain amide of Gln19 forms an oxyanion hole, which would stabilize the carbonyl oxygen of substrate, or the tetrahedral intermediate.

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.