DB code: S00461

RLCP classification 1.40.14550.574 : Hydrolysis
CATH domain 3.90.245.10 : Inosine-uridine Nucleoside N-ribohydrolase; Chain A Catalytic domain
E.C. 3.2.2.-
CSA 1mas
M-CSA 1mas
MACiE M0039

CATH domain Related DB codes (homologues)
3.90.245.10 : Inosine-uridine Nucleoside N-ribohydrolase; Chain A S00751 S00910

Uniprot Enzyme Name
UniprotKB Protein name Synonyms Pfam
P83851 Inosine-uridine preferring nucleoside hydrolase
IU-nucleoside hydrolase
IU-NH
EC 3.2.2.-
Purine nucleosidase
Non-specific nucleoside hydrolase
PF01156 (IU_nuc_hydro)
[Graphical View]
Q27546 Inosine-uridine preferring nucleoside hydrolase
IU-nucleoside hydrolase
IU-NH
EC 3.2.2.-
Purine nucleosidase
Non-specific nucleoside hydrolase
PF01156 (IU_nuc_hydro)
[Graphical View]

KEGG enzyme name
inosine-uridine preferring nucleoside hydrolase
IU-NH
IU-nucleoside hydrolase
non-specific nucleoside hydrolase
purine nucleosidase

UniprotKB: Accession Number Entry name Activity Subunit Subcellular location Cofactor
P83851 IUNH_LEIMA A purine nucleoside + H(2)O = D-ribose + a purine base. Homotetramer. Calcium.
Q27546 IUNH_CRIFA A purine nucleoside + H(2)O = D-ribose + a purine base. Homotetramer. Calcium.

KEGG Pathways
Map code Pathways E.C.
MAP00230 Purine metabolism
MAP00760 Nicotinate and nicotinamide metabolism

Compound table
Cofactors Substrates Products Intermediates
KEGG-id C00076 C15586 C00001 C15587 C00121
E.C.
Compound Calcium N-D-Ribosylpurine H2O Purine D-Ribose
Type divalent metal (Ca2+, Mg2+) nucleoside H2O aromatic ring (with nitrogen atoms) carbohydrate
ChEBI 29108
18255
15377
17258
35586
35588
35589
47013
PubChem 271
68368
22247451
962
1044
5779
1ezrA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:_CA Unbound Unbound Unbound
1ezrB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:_CA Unbound Unbound Unbound
1ezrC Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:_CA Unbound Unbound Unbound
1ezrD Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:_CA Unbound Unbound Unbound
1masA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Analogue:__K Unbound Unbound Unbound
1masB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Analogue:__K Unbound Unbound Unbound
2masA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:_CA Analogue:PIR Unbound Unbound
2masB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:_CA Analogue:PIR Unbound Unbound
2masC Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:_CA Analogue:PIR Unbound Unbound
2masD Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:_CA Analogue:PIR Unbound Unbound

Reference for Active-site residues
resource references E.C.

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
1ezrA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 10;HIS 82;HIS 240 ASP 10;ASP 15;THR 126;ASP 241(Ca2+ binding)
1ezrB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 10;HIS 82;HIS 240 ASP 10;ASP 15;THR 126;ASP 241(Ca2+ binding)
1ezrC Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 10;HIS 82;HIS 240 ASP 10;ASP 15;THR 126;ASP 241(Ca2+ binding)
1ezrD Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 10;HIS 82;HIS 240 ASP 10;ASP 15;THR 126;ASP 241(Ca2+ binding)
1masA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 10; ;HIS 241 ASP 10;ASP 15;THR 126;ASP 242(Ca2+ binding) invisible H82
1masB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 10; ;HIS 241 ASP 10;ASP 15;THR 126;ASP 242(Ca2+ binding) invisible H82
2masA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 10;HIS 82;HIS 241 ASP 10;ASP 15;THR 126;ASP 242(Ca2+ binding)
2masB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 10;HIS 82;HIS 241 ASP 10;ASP 15;THR 126;ASP 242(Ca2+ binding)
2masC Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 10;HIS 82;HIS 241 ASP 10;ASP 15;THR 126;ASP 242(Ca2+ binding)
2masD Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 10;HIS 82;HIS 241 ASP 10;ASP 15;THR 126;ASP 242(Ca2+ binding)

References for Catalytic Mechanism
References Sections No. of steps in catalysis
[2]
p.5968-5970, Fig.7
[3]
p.5979
[4]
p.21717-21719
[5]
p.3533-3534
[6]
Fig.1, p.6279, p.6283 2
[7]
p.21117-21120
[9]
p.1368-1375
[10]
p.15943-15944, p.15945
[11]
Scheme 1, p.8830-8833 2
[12]
Scheme 1, p.14598-14600 2

References
[1]
Resource
Comments
Medline ID
PubMed ID 7577992
Journal Biochemistry
Year 1995
Volume 34
Pages 13961-6
Authors Parkin DW, Schramm VL
Title Binding modes for substrate and a proposed transition-state analogue of protozoan nucleoside hydrolase.
Related PDB
Related UniProtKB
[2]
Resource
Comments
Medline ID
PubMed ID 8634237
Journal Biochemistry
Year 1996
Volume 35
Pages 5963-70
Authors Gopaul DN, Meyer SL, Degano M, Sacchettini JC, Schramm VL
Title Inosine-uridine nucleoside hydrolase from Crithidia fasciculata. Genetic characterization, crystallization, and identification of histidine 241 as a catalytic site residue.
Related PDB
Related UniProtKB
[3]
Resource
Comments X-ray crystallography (2.5 Angstroms)
Medline ID
PubMed ID 8634238
Journal Biochemistry
Year 1996
Volume 35
Pages 5971-5981
Authors Degano M, Gopaul DN, Scapin G, Schramm VL, Sacchettini JC
Title Three-dimensional structure of the inosine-uridine nucleoside N-ribohydrolase from Crithidia fasciculata.
Related PDB 1mas
Related UniProtKB
[4]
Resource
Comments
Medline ID
PubMed ID 8702965
Journal J Biol Chem
Year 1996
Volume 271
Pages 21713-9
Authors Parkin DW
Title Purine-specific nucleoside N-ribohydrolase from Trypanosoma brucei brucei. Purification, specificity, and kinetic mechanism.
Related PDB
Related UniProtKB
[5]
Resource
Comments
Medline ID
PubMed ID 9132003
Journal Biochemistry
Year 1997
Volume 36
Pages 3528-34
Authors Parkin DW, Limberg G, Tyler PC, Furneaux RH, Chen XY, Schramm VL
Title Isozyme-specific transition state inhibitors for the trypanosomal nucleoside hydrolases.
Related PDB
Related UniProtKB
[6]
Resource
Comments X-ray crystallography (2.3 Angstroms)
Medline ID
PubMed ID 9572842
Journal Biochemistry
Year 1998
Volume 37
Pages 6277-6285
Authors Degano M, Almo SC, Sacchettini JC, Schramm VL
Title Trypanosomal nucleoside hydrolase. A novel mechanism from the structure with a transition-state inhibitor.
Related PDB 2mas
Related UniProtKB
[7]
Resource
Comments X-ray crystallography (2.5 Angstroms)
Medline ID
PubMed ID 10409664
Journal J Biol Chem
Year 1999
Volume 274
Pages 21114-21120
Authors Shi W, Schramm VL, Almo SC
Title Nucleoside hydrolase from Leishmania major. Cloning, expression, catalytic properties, transition state inhibitors, and the 2.5-a crystal structure.
Related PDB 1ezr
Related UniProtKB
[8]
Resource
Comments
Medline ID
PubMed ID 11282633
Journal Appl Environ Microbiol
Year 2001
Volume 67
Pages 1783-7
Authors Ogawa J, Takeda S, Xie SX, Hatanaka H, Ashikari T, Amachi T, Shimizu S
Title Purification, characterization, and gene cloning of purine nucleosidase from Ochrobactrum anthropi.
Related PDB
Related UniProtKB
[9]
Resource
Comments
Medline ID
PubMed ID 11292348
Journal J Mol Biol
Year 2001
Volume 307
Pages 1363-79
Authors Versees W, Decanniere K, Pelle R, Depoorter J, Brosens E, Parkin DW, Steyaert J
Title Structure and function of a novel purine specific nucleoside hydrolase from Trypanosoma vivax.
Related PDB
Related UniProtKB
[10]
Resource
Comments
Medline ID
PubMed ID 11854281
Journal J Biol Chem
Year 2002
Volume 277
Pages 15938-46
Authors Versees W, Decanniere K, Van Holsbeke E, Devroede N, Steyaert J
Title Enzyme-substrate interactions in the purine-specific nucleoside hydrolase from Trypanosoma vivax.
Related PDB
Related UniProtKB
[11]
Resource
Comments
Medline ID
PubMed ID 12137535
Journal J Am Chem Soc
Year 2002
Volume 124
Pages 8825-33
Authors Mazumder D, Kahn K, Bruice TC
Title Computer simulations of trypanosomal nucleoside hydrolase: determination of the protonation state of the bound transition-state analogue.
Related PDB
Related UniProtKB
[12]
Resource
Comments
Medline ID
PubMed ID 12465969
Journal J Am Chem Soc
Year 2002
Volume 124
Pages 14591-600
Authors Mazumder D, Bruice TC
Title Exploring nucleoside hydrolase catalysis in silico: molecular dynamics study of enzyme-bound substrate and transition state.
Related PDB
Related UniProtKB

Comments
This enzyme belongs to the IU-nuceloside hydrolase family. This enzyme is homologous to ribosylpyrimidine nucleosidase (EC 3.2.2.8; S00751 in EzCatDB).
According to the literature [2] & [4], The oxocarbonium ion is formed in the transition state, which is characterstic of an SN1-like catalytic mechanism.
The paper [3] on crystal structure suggested that His241 can act as proton donor for the leaving nitrogenous base, whilst the paper [5] mentioned that His82 as well as His241 can protonates the leaving group. Asp14 is reported to have a hydrogen-bonding interaction with His241 [3].
Moreover, the papers [5], [6] and [7] suggested that metal or Ca2+ -bound water can attack the C1' atom after the oxocarbonium ion has been formed. One of the aspartic acid residues, Asp10, Asp15, Thr126 and Asp242, is proposed to be the group which will act as a general base, extracting the proton from the incoming water nucleophile, according to the paper [3]. The paper [12] based on molecular simulation suggested that the proton will be transferred from the activated water through Asp10 to Asp15 to water pool.

Created Updated
2002-07-11 2011-09-27