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 15377
PubChem			22247451 962 22247451 962

1aecA	Unbound	Unbound		Unbound	Unbound	Unbound	Unbound	Intermediate-analogue:E64
2actA	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	GLN 19;CYS 25;HIS 162;ASN 182			CYS 25
2actA	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.

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