EzCatDB: S00461
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DB codeS00461
RLCP classification1.40.14550.574 : Hydrolysis
CATH domainDomain 13.90.245.10 : Inosine-uridine Nucleoside N-ribohydrolase; Chain ACatalytic domain
E.C.3.2.2.-
CSA1mas
MACiEM0039

CATH domainRelated DB codes (homologues)
3.90.245.10 : Inosine-uridine Nucleoside N-ribohydrolase; Chain AS00751,S00910

Enzyme Name
UniProtKBKEGG

P83851Q27546
Protein nameInosine-uridine preferring nucleoside hydrolaseInosine-uridine preferring nucleoside hydrolaseinosine-uridine preferring nucleoside hydrolase
IU-NH
IU-nucleoside hydrolase
non-specific nucleoside hydrolase
purine nucleosidase
SynonymsIU-nucleoside hydrolase
IU-NH
EC 3.2.2.-
Purine nucleosidase
Non-specific nucleoside hydrolase
IU-nucleoside hydrolase
IU-NH
EC 3.2.2.-
Purine nucleosidase
Non-specific nucleoside hydrolase
PfamPF01156 (IU_nuc_hydro)
[Graphical view]
PF01156 (IU_nuc_hydro)
[Graphical view]

KEGG pathways
MAP codePathways
MAP00230Purine metabolism
MAP00760Nicotinate and nicotinamide metabolism

UniProtKB:Accession NumberP83851Q27546
Entry nameIUNH_LEIMAIUNH_CRIFA
ActivityA purine nucleoside + H(2)O = D-ribose + a purine base.A purine nucleoside + H(2)O = D-ribose + a purine base.
SubunitHomotetramer.Homotetramer.
Subcellular location

CofactorCalcium.Calcium.

Compound table: links to PDB-related databases & PoSSuM

CofactorsSubstratesProducts
KEGG-idC00076C15586C00001C15587C00121
CompoundCalciumN-D-RibosylpurineH2OPurineD-Ribose
Typedivalent metal (Ca2+, Mg2+)nucleosideH2Oaromatic ring (with nitrogen atoms)carbohydrate
ChEBI29108
18255
15377
35589
35588
35586
17258
47013
PubChem271
68368
962
22247451
1044
5779
             
1ezrABound:_CAUnbound UnboundUnbound
1ezrBBound:_CAUnbound UnboundUnbound
1ezrCBound:_CAUnbound UnboundUnbound
1ezrDBound:_CAUnbound UnboundUnbound
1masAAnalogue:__KUnbound UnboundUnbound
1masBAnalogue:__KUnbound UnboundUnbound
2masABound:_CAAnalogue:PIR UnboundUnbound
2masBBound:_CAAnalogue:PIR UnboundUnbound
2masCBound:_CAAnalogue:PIR UnboundUnbound
2masDBound:_CAAnalogue:PIR UnboundUnbound

Active-site residues
pdbCatalytic residuesCofactor-binding residuescomment
           
1ezrAASP 10;HIS 82;HIS 240
ASP 10;ASP 15;THR 126;ASP 241(Ca2+ binding)
 
1ezrBASP 10;HIS 82;HIS 240
ASP 10;ASP 15;THR 126;ASP 241(Ca2+ binding)
 
1ezrCASP 10;HIS 82;HIS 240
ASP 10;ASP 15;THR 126;ASP 241(Ca2+ binding)
 
1ezrDASP 10;HIS 82;HIS 240
ASP 10;ASP 15;THR 126;ASP 241(Ca2+ binding)
 
1masAASP 10;      ;HIS 241
ASP 10;ASP 15;THR 126;ASP 242(Ca2+ binding)
invisible H82
1masBASP 10;      ;HIS 241
ASP 10;ASP 15;THR 126;ASP 242(Ca2+ binding)
invisible H82
2masAASP 10;HIS 82;HIS 241
ASP 10;ASP 15;THR 126;ASP 242(Ca2+ binding)
 
2masBASP 10;HIS 82;HIS 241
ASP 10;ASP 15;THR 126;ASP 242(Ca2+ binding)
 
2masCASP 10;HIS 82;HIS 241
ASP 10;ASP 15;THR 126;ASP 242(Ca2+ binding)
 
2masDASP 10;HIS 82;HIS 241
ASP 10;ASP 15;THR 126;ASP 242(Ca2+ binding)
 

References for Catalytic Mechanism
ReferencesSectionsNo. 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.62832
[7]p.21117-21120
[9]p.1368-1375
[10]p.15943-15944, p.15945
[11]Scheme 1, p.8830-88332
[12]Scheme 1, p.14598-146002

references
[1]
PubMed ID7577992
JournalBiochemistry
Year1995
Volume34
Pages13961-6
AuthorsParkin DW, Schramm VL
TitleBinding modes for substrate and a proposed transition-state analogue of protozoan nucleoside hydrolase.
[2]
PubMed ID8634237
JournalBiochemistry
Year1996
Volume35
Pages5963-70
AuthorsGopaul DN, Meyer SL, Degano M, Sacchettini JC, Schramm VL
TitleInosine-uridine nucleoside hydrolase from Crithidia fasciculata. Genetic characterization, crystallization, and identification of histidine 241 as a catalytic site residue.
[3]
CommentsX-ray crystallography (2.5 Angstroms)
PubMed ID8634238
JournalBiochemistry
Year1996
Volume35
Pages5971-5981
AuthorsDegano M, Gopaul DN, Scapin G, Schramm VL, Sacchettini JC
TitleThree-dimensional structure of the inosine-uridine nucleoside N-ribohydrolase from Crithidia fasciculata.
Related PDB1mas
[4]
PubMed ID8702965
JournalJ Biol Chem
Year1996
Volume271
Pages21713-9
AuthorsParkin DW
TitlePurine-specific nucleoside N-ribohydrolase from Trypanosoma brucei brucei. Purification, specificity, and kinetic mechanism.
[5]
PubMed ID9132003
JournalBiochemistry
Year1997
Volume36
Pages3528-34
AuthorsParkin DW, Limberg G, Tyler PC, Furneaux RH, Chen XY, Schramm VL
TitleIsozyme-specific transition state inhibitors for the trypanosomal nucleoside hydrolases.
[6]
CommentsX-ray crystallography (2.3 Angstroms)
PubMed ID9572842
JournalBiochemistry
Year1998
Volume37
Pages6277-6285
AuthorsDegano M, Almo SC, Sacchettini JC, Schramm VL
TitleTrypanosomal nucleoside hydrolase. A novel mechanism from the structure with a transition-state inhibitor.
Related PDB2mas
[7]
CommentsX-ray crystallography (2.5 Angstroms)
PubMed ID10409664
JournalJ Biol Chem
Year1999
Volume274
Pages21114-21120
AuthorsShi W, Schramm VL, Almo SC
TitleNucleoside hydrolase from Leishmania major. Cloning, expression, catalytic properties, transition state inhibitors, and the 2.5-a crystal structure.
Related PDB1ezr
[8]
PubMed ID11282633
JournalAppl Environ Microbiol
Year2001
Volume67
Pages1783-7
AuthorsOgawa J, Takeda S, Xie SX, Hatanaka H, Ashikari T, Amachi T, Shimizu S
TitlePurification, characterization, and gene cloning of purine nucleosidase from Ochrobactrum anthropi.
[9]
PubMed ID11292348
JournalJ Mol Biol
Year2001
Volume307
Pages1363-79
AuthorsVersees W, Decanniere K, Pelle R, Depoorter J, Brosens E, Parkin DW, Steyaert J
TitleStructure and function of a novel purine specific nucleoside hydrolase from Trypanosoma vivax.
[10]
PubMed ID11854281
JournalJ Biol Chem
Year2002
Volume277
Pages15938-46
AuthorsVersees W, Decanniere K, Van Holsbeke E, Devroede N, Steyaert J
TitleEnzyme-substrate interactions in the purine-specific nucleoside hydrolase from Trypanosoma vivax.
[11]
PubMed ID12137535
JournalJ Am Chem Soc
Year2002
Volume124
Pages8825-33
AuthorsMazumder D, Kahn K, Bruice TC
TitleComputer simulations of trypanosomal nucleoside hydrolase: determination of the protonation state of the bound transition-state analogue.
[12]
PubMed ID12465969
JournalJ Am Chem Soc
Year2002
Volume124
Pages14591-600
AuthorsMazumder D, Bruice TC
TitleExploring nucleoside hydrolase catalysis in silico: molecular dynamics study of enzyme-bound substrate and transition state.

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.

createdupdated
2002-07-112011-09-27
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 - )
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