S00461
type: Enzyme
rlcp: p574
cath: Inosine-uridine Nucleoside N-ribohydrolase; Chain A
ec: https://purl.uniprot.org/enzyme/3.2.2.-
csa: 1mas
macie: M0039
uniprot: P83851
uniprot: Q27546
kegg enzyme: inosine-uridine preferring nucleoside hydrolase
kegg enzyme: IU-NH
kegg enzyme: IU-nucleoside hydrolase
kegg enzyme: non-specific nucleoside hydrolase
kegg enzyme: purine nucleosidase
kegg pathway: Purine metabolism
kegg pathway: Nicotinate and nicotinamide metabolism
kegg cofactor: Calcium
kegg substrate: N-D-Ribosylpurine
kegg substrate: H2O
kegg product: Purine
kegg product: D-Ribose
pdb: 1ezrA
pdb: 1ezrB
pdb: 1ezrC
pdb: 1ezrD
pdb: 1masA
pdb: 1masB
pdb: 2masA
pdb: 2masB
pdb: 2masC
pdb: 2masD
pdb bound state: Unbound
  compound: N-D-Ribosylpurine
  pdb: 1ezrA
pdb bound state: Unbound
  compound: N-D-Ribosylpurine
  pdb: 1ezrB
pdb bound state: Unbound
  compound: N-D-Ribosylpurine
  pdb: 1ezrC
pdb bound state: Unbound
  compound: N-D-Ribosylpurine
  pdb: 1ezrD
pdb bound state: Unbound
  compound: N-D-Ribosylpurine
  pdb: 1masA
pdb bound state: Unbound
  compound: N-D-Ribosylpurine
  pdb: 1masB
pdb bound state: Analogue
  compound: N-D-Ribosylpurine
  pdb: 2masA
  ligand het code: PIR
pdb bound state: Analogue
  compound: N-D-Ribosylpurine
  pdb: 2masB
  ligand het code: PIR
pdb bound state: Analogue
  compound: N-D-Ribosylpurine
  pdb: 2masC
  ligand het code: PIR
pdb bound state: Analogue
  compound: N-D-Ribosylpurine
  pdb: 2masD
  ligand het code: PIR
pdb bound state: Analogue
  compound: Calcium
  pdb: 1masA
  ligand het code: __K
pdb bound state: Analogue
  compound: Calcium
  pdb: 1masB
  ligand het code: __K
pdb bound state: Unbound
  compound: Purine
  pdb: 1ezrA
pdb bound state: Unbound
  compound: Purine
  pdb: 1ezrB
pdb bound state: Unbound
  compound: Purine
  pdb: 1ezrC
pdb bound state: Unbound
  compound: Purine
  pdb: 1ezrD
pdb bound state: Unbound
  compound: Purine
  pdb: 1masA
pdb bound state: Unbound
  compound: Purine
  pdb: 1masB
pdb bound state: Unbound
  compound: Purine
  pdb: 2masA
pdb bound state: Unbound
  compound: Purine
  pdb: 2masB
pdb bound state: Unbound
  compound: Purine
  pdb: 2masC
pdb bound state: Unbound
  compound: Purine
  pdb: 2masD
pdb bound state: Unbound
  compound: D-Ribose
  pdb: 1ezrA
pdb bound state: Unbound
  compound: D-Ribose
  pdb: 1ezrB
pdb bound state: Unbound
  compound: D-Ribose
  pdb: 1ezrC
pdb bound state: Unbound
  compound: D-Ribose
  pdb: 1ezrD
pdb bound state: Unbound
  compound: D-Ribose
  pdb: 1masA
pdb bound state: Unbound
  compound: D-Ribose
  pdb: 1masB
pdb bound state: Unbound
  compound: D-Ribose
  pdb: 2masA
pdb bound state: Unbound
  compound: D-Ribose
  pdb: 2masB
pdb bound state: Unbound
  compound: D-Ribose
  pdb: 2masC
pdb bound state: Unbound
  compound: D-Ribose
  pdb: 2masD
reference for catalytic mechanism: ReferenceForCatalyticMechanism
  reference index: 2
  reference section: p.5968-5970, Fig.7
reference for catalytic mechanism: ReferenceForCatalyticMechanism
  reference index: 3
  reference section: p.5979
reference for catalytic mechanism: ReferenceForCatalyticMechanism
  reference index: 4
  reference section: p.21717-21719
reference for catalytic mechanism: ReferenceForCatalyticMechanism
  reference index: 5
  reference section: p.3533-3534
reference for catalytic mechanism: ReferenceForCatalyticMechanism
  reference index: 6
  reference section: Fig.1, p.6279, p.6283
  reference step: 2
references: Binding modes for substrate and a proposed transition-state analogue of protozoan nucleoside hydrolase.
references: Inosine-uridine nucleoside hydrolase from Crithidia fasciculata. Genetic characterization, crystallization, and identification of histidine 241 as a catalytic site residue.
references: Three-dimensional structure of the inosine-uridine nucleoside N-ribohydrolase from Crithidia fasciculata.
references: Purine-specific nucleoside N-ribohydrolase from Trypanosoma brucei brucei. Purification, specificity, and kinetic mechanism.
references: Isozyme-specific transition state inhibitors for the trypanosomal nucleoside hydrolases.
references: Trypanosomal nucleoside hydrolase. A novel mechanism from the structure with a transition-state inhibitor.
references: Nucleoside hydrolase from Leishmania major. Cloning, expression, catalytic properties, transition state inhibitors, and the 2.5-a crystal structure.
references: Purification, characterization, and gene cloning of purine nucleosidase from Ochrobactrum anthropi.
references: Structure and function of a novel purine specific nucleoside hydrolase from Trypanosoma vivax.
references: Enzyme-substrate interactions in the purine-specific nucleoside hydrolase from Trypanosoma vivax.
references: Computer simulations of trypanosomal nucleoside hydrolase: determination of the protonation state of the bound transition-state analogue.
references: Exploring nucleoside hydrolase catalysis in silico: molecular dynamics study of enzyme-bound substrate and transition state.
comment: 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.

Inosine-uridine Nucleoside N-ribohydrolase; Chain A
type: Cath
references: http://www.cathdb.info/version/latest/superfamily/3.90.245.10
catalytic domain: index.html

Purine metabolism
type: KeggPathway
references: KEGG:MAP00230

Nicotinate and nicotinamide metabolism
type: KeggPathway
references: KEGG:MAP00760

Calcium
type: KeggCofactor
references: KEGG:C00076
compound type: divalent metal (Ca2+, Mg2+)
references: CHEBI:29108
references: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi

N-D-Ribosylpurine
type: KeggSubstrate
references: KEGG:C15586
compound type: nucleoside
references: CHEBI:18255
references: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi

H2O
type: KeggSubstrate
references: KEGG:C00001
compound type: H2O
references: CHEBI:15377
references: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi

Purine
type: KeggProduct
references: KEGG:C15587
compound type: aromatic ring (with nitrogen atoms)
references: CHEBI:17258
references: CHEBI:35586
references: CHEBI:35588
references: CHEBI:35589
references: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi

D-Ribose
type: KeggProduct
references: KEGG:C00121
compound type: carbohydrate
references: CHEBI:47013
references: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi

1ezrA
type: Pdb
references: 1ezr
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1ezr
catalytic residue: ASP 10;HIS 82;HIS 240
cofactor binding residue: ASP 10;ASP 15;THR 126;ASP 241(Ca2+ binding)

1ezrB
type: Pdb
references: 1ezr
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1ezr
catalytic residue: ASP 10;HIS 82;HIS 240
cofactor binding residue: ASP 10;ASP 15;THR 126;ASP 241(Ca2+ binding)

1ezrC
type: Pdb
references: 1ezr
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1ezr
catalytic residue: ASP 10;HIS 82;HIS 240
cofactor binding residue: ASP 10;ASP 15;THR 126;ASP 241(Ca2+ binding)

1ezrD
type: Pdb
references: 1ezr
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1ezr
catalytic residue: ASP 10;HIS 82;HIS 240
cofactor binding residue: ASP 10;ASP 15;THR 126;ASP 241(Ca2+ binding)

1masA
type: Pdb
references: 1mas
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1mas
catalytic residue: ASP 10; ;HIS 241
cofactor binding residue: ASP 10;ASP 15;THR 126;ASP 242(Ca2+ binding)
comment: invisible H82

1masB
type: Pdb
references: 1mas
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1mas
catalytic residue: ASP 10; ;HIS 241
cofactor binding residue: ASP 10;ASP 15;THR 126;ASP 242(Ca2+ binding)
comment: invisible H82

2masA
type: Pdb
references: 2mas
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:2mas
catalytic residue: ASP 10;HIS 82;HIS 241
cofactor binding residue: ASP 10;ASP 15;THR 126;ASP 242(Ca2+ binding)

2masB
type: Pdb
references: 2mas
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:2mas
catalytic residue: ASP 10;HIS 82;HIS 241
cofactor binding residue: ASP 10;ASP 15;THR 126;ASP 242(Ca2+ binding)

2masC
type: Pdb
references: 2mas
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:2mas
catalytic residue: ASP 10;HIS 82;HIS 241
cofactor binding residue: ASP 10;ASP 15;THR 126;ASP 242(Ca2+ binding)

2masD
type: Pdb
references: 2mas
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:2mas
catalytic residue: ASP 10;HIS 82;HIS 241
cofactor binding residue: ASP 10;ASP 15;THR 126;ASP 242(Ca2+ binding)

Binding modes for substrate and a proposed transition-state analogue of protozoan nucleoside hydrolase.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/7577992
journal: Biochemistry
volume: 34
pages: 13961-6
published year: 1995
authors:
  item: Parkin DW
  item: Schramm VL

Inosine-uridine nucleoside hydrolase from Crithidia fasciculata. Genetic characterization, crystallization, and identification of histidine 241 as a catalytic site residue.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/8634237
journal: Biochemistry
volume: 35
pages: 5963-70
published year: 1996
authors:
  item: Gopaul DN
  item: Meyer SL
  item: Degano M
  item: Sacchettini JC
  item: Schramm VL

Three-dimensional structure of the inosine-uridine nucleoside N-ribohydrolase from Crithidia fasciculata.
type: BibliographicResource
comment: X-ray crystallography (2.5 Angstroms)
references: http://www.ncbi.nlm.nih.gov/pubmed/8634238
journal: Biochemistry
volume: 35
pages: 5971-5981
published year: 1996
authors:
  item: Degano M
  item: Gopaul DN
  item: Scapin G
  item: Schramm VL
  item: Sacchettini JC
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl

Purine-specific nucleoside N-ribohydrolase from Trypanosoma brucei brucei. Purification, specificity, and kinetic mechanism.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/8702965
journal: J Biol Chem
volume: 271
pages: 21713-9
published year: 1996
authors:
  item: Parkin DW

Isozyme-specific transition state inhibitors for the trypanosomal nucleoside hydrolases.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/9132003
journal: Biochemistry
volume: 36
pages: 3528-34
published year: 1997
authors:
  item: Parkin DW
  item: Limberg G
  item: Tyler PC
  item: Furneaux RH
  item: Chen XY
  item: Schramm VL

Trypanosomal nucleoside hydrolase. A novel mechanism from the structure with a transition-state inhibitor.
type: BibliographicResource
comment: X-ray crystallography (2.3 Angstroms)
references: http://www.ncbi.nlm.nih.gov/pubmed/9572842
journal: Biochemistry
volume: 37
pages: 6277-6285
published year: 1998
authors:
  item: Degano M
  item: Almo SC
  item: Sacchettini JC
  item: Schramm VL
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl

Nucleoside hydrolase from Leishmania major. Cloning, expression, catalytic properties, transition state inhibitors, and the 2.5-a crystal structure.
type: BibliographicResource
comment: X-ray crystallography (2.5 Angstroms)
references: http://www.ncbi.nlm.nih.gov/pubmed/10409664
journal: J Biol Chem
volume: 274
pages: 21114-21120
published year: 1999
authors:
  item: Shi W
  item: Schramm VL
  item: Almo SC
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl

Purification, characterization, and gene cloning of purine nucleosidase from Ochrobactrum anthropi.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/11282633
journal: Appl Environ Microbiol
volume: 67
pages: 1783-7
published year: 2001
authors:
  item: Ogawa J
  item: Takeda S
  item: Xie SX
  item: Hatanaka H
  item: Ashikari T
  item: Amachi T
  item: Shimizu S

Structure and function of a novel purine specific nucleoside hydrolase from Trypanosoma vivax.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/11292348
journal: J Mol Biol
volume: 307
pages: 1363-79
published year: 2001
authors:
  item: Versees W
  item: Decanniere K
  item: Pelle R
  item: Depoorter J
  item: Brosens E
  item: Parkin DW
  item: Steyaert J

Enzyme-substrate interactions in the purine-specific nucleoside hydrolase from Trypanosoma vivax.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/11854281
journal: J Biol Chem
volume: 277
pages: 15938-46
published year: 2002
authors:
  item: Versees W
  item: Decanniere K
  item: Van Holsbeke E
  item: Devroede N
  item: Steyaert J

Computer simulations of trypanosomal nucleoside hydrolase: determination of the protonation state of the bound transition-state analogue.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/12137535
journal: J Am Chem Soc
volume: 124
pages: 8825-33
published year: 2002
authors:
  item: Mazumder D
  item: Kahn K
  item: Bruice TC

Exploring nucleoside hydrolase catalysis in silico: molecular dynamics study of enzyme-bound substrate and transition state.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/12465969
journal: J Am Chem Soc
volume: 124
pages: 14591-600
published year: 2002
authors:
  item: Mazumder D
  item: Bruice TC

ReferenceForCatalyticMechanism
reference index: 7
reference section: p.21117-21120

ReferenceForCatalyticMechanism
reference index: 9
reference section: p.1368-1375

ReferenceForCatalyticMechanism
reference index: 10
reference section: p.15943-15944, p.15945

ReferenceForCatalyticMechanism
reference index: 11
reference section: Scheme 1, p.8830-8833
reference step: 2

ReferenceForCatalyticMechanism
reference index: 12
reference section: Scheme 1, p.14598-14600
reference step: 2