DB code: S00447

RLCP classification 1.13.30000.44 : Hydrolysis
CATH domain 3.90.70.10 : Cathepsin B; Chain A Catalytic domain
E.C. 3.4.22.14
CSA
M-CSA
MACiE

CATH domain Related DB codes (homologues)
3.90.70.10 : Cathepsin B; Chain A S00444 S00445 S00448 S00449 S00450 S00451 S00446 S00518

Uniprot Enzyme Name
UniprotKB Protein name Synonyms MEROPS Pfam
P00785 Actinidain (Actinidin) (EC 3.4.22.14)AltName: Allergen=Act c 1;
None I29.003 ()
PF08246 (Inhibitor_I29)
PF00112 (Peptidase_C1)
[Graphical View]

KEGG enzyme name
actinidain
actinidin
Actinidia anionic protease
proteinase A2 of Actinidia chinensis

UniprotKB: Accession Number Entry name Activity Subunit Subcellular location Cofactor
P00785 ACTN_ACTCH Specificity close to that of papain.

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 22247451
962
1aecA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Intermediate-analogue:E64
2actA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound

Reference for Active-site residues
resource references E.C.
Swiss-prot;P00785 & literature [2]

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
1aecA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain GLN 19;CYS 25;HIS 162;ASN 182 CYS 25
2actA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain GLN 19;CYS 25;HIS 162;ASN 182 CYS 25

References for Catalytic Mechanism
References Sections No. of steps in catalysis
[2]
p.469-476
[3]
p.5174-5175

References
[1]
Resource
Comments X-ray crystallography (1.7 Angstroms)
Medline ID
PubMed ID not found
Journal Acta Crystallogr.,Sect.A
Year 1980
Volume 36
Pages 559
Authors E.N.Baker,E.J.Dodson
Title Crystallographic refinement of the structure of actinidin at 1.7 angstroms resolution by fast fourier least-*squares methods.
Related PDB 2act
Related UniProtKB
[2]
Resource
Comments X-ray crystallography (1.7 Angstroms)
Medline ID 81072298
PubMed ID 7003158
Journal J Mol Biol
Year 1980
Volume 141
Pages 441-84
Authors Baker EN
Title Structure of actinidin, after refinement at 1.7 A resolution.
Related PDB
Related UniProtKB P00785
[3]
Resource
Comments X-ray crystallography (1.86 Angstroms)
Medline ID
PubMed ID 1606141
Journal Biochemistry
Year 1992
Volume 31
Pages 5172-6
Authors Varughese KI, Su Y, Cromwell D, Hasnain S, Xuong NH
Title Crystal structure of an actinidin-E-64 complex.
Related PDB 1aec
Related UniProtKB
[4]
Resource
Comments
Medline ID
PubMed ID 7958276
Journal Biochem Soc Trans
Year 1994
Volume 22
Pages 214S
Authors Patel M, Thomas MP, Noble MA, Gul S, Thomas EW, Brocklehurst K
Title Variation in the effects of P2-S2 binding contacts on catalytic site chemistry among members of the cysteine proteinase family.
Related PDB
Related UniProtKB
[5]
Resource
Comments
Medline ID
PubMed ID 9649846
Journal Biochem Soc Trans
Year 1998
Volume 26
Pages S171
Authors Gul S, Pinitglang S, Thomas EW, Verma C, Brocklehurst K
Title Sensitivities of transition state geometries to P1-P2 binding in reactions of papain and actinidin.
Related PDB
Related UniProtKB
[6]
Resource
Comments
Medline ID
PubMed ID 9649848
Journal Biochem Soc Trans
Year 1998
Volume 26
Pages S173
Authors Reid JD, Sreedharan S, Cole A, Maskell S, Bokth A, Thomas EW, Brocklehurst K
Title Detection of a free enzyme isomerisation in actinidin catalysed hydrolysis.
Related PDB
Related UniProtKB
[7]
Resource
Comments
Medline ID
PubMed ID 11439083
Journal Biochem J
Year 2001
Volume 357
Pages 343-52
Authors Reid JD, Hussain S, Sreedharan SK, Bailey TS, Pinitglang S, Thomas EW, Verma CS, Brocklehurst K
Title Variation in aspects of cysteine proteinase catalytic mechanism deduced by spectroscopic observation of dithioester intermediates, kinetic analysis and molecular dynamics simulations.
Related PDB
Related UniProtKB
[8]
Resource
Comments
Medline ID
PubMed ID 12643810
Journal Biochem J
Year 2003
Volume 372
Pages 735-46
Authors Hussain S, Pinitglang S, Bailey TS, Reid JD, Noble MA, Resmini M, Thomas EW, Greaves RB, Verma CS, Brocklehurst K
Title Variation 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.
Related PDB
Related UniProtKB

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.

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