S00924
type: Enzyme
rlcp: p1168
cath: Nucleoside Triphosphate Pyrophosphohydrolase
ec: https://purl.uniprot.org/enzyme/3.6.1.13
ec: https://purl.uniprot.org/enzyme/3.6.1.58
uniprot: Q9UKK9
kegg enzyme: ADP-ribose diphosphatase
  type: KeggEnzyme
  ec: https://purl.uniprot.org/enzyme/3.6.1.13
kegg enzyme: ADPribose pyrophosphatase
  type: KeggEnzyme
  ec: https://purl.uniprot.org/enzyme/3.6.1.13
kegg enzyme: Adenosine diphosphoribose pyrophosphatase
  type: KeggEnzyme
  ec: https://purl.uniprot.org/enzyme/3.6.1.13
kegg enzyme: ADPR-PPase
  type: KeggEnzyme
  ec: https://purl.uniprot.org/enzyme/3.6.1.13
kegg enzyme: 8-oxo-dGDP phosphatase
  type: KeggEnzyme
  ec: https://purl.uniprot.org/enzyme/3.6.1.58
kegg enzyme: NUDT5
  type: KeggEnzyme
  ec: https://purl.uniprot.org/enzyme/3.6.1.58
kegg pathway: Purine metabolism
kegg cofactor: Magnesium
kegg substrate: ADP-ribose
kegg substrate: 8-Oxo-dGDP
kegg substrate: H2O
kegg product: AMP
kegg product: D-ribose 5-phosphate
kegg product: 8-Oxo-dGMP
kegg product: Orthophosphate
pdb: 2dsbA00
pdb: 2dsbB00
pdb: 2dsbC00
pdb: 2dsbD00
pdb: 2dscA00
pdb: 2dscB00
pdb: 2dsdA00
pdb: 2dsdB00
pdb: 3ac9A00
pdb: 3ac9B00
pdb: 3acaA00
pdb: 3acaB00
pdb: 3bm4A00
pdb: 3bm4B00
pdb: 3l85A00
pdb: 3l85B00
pdb bound state: Unbound
  compound: ADP-ribose
  pdb: 2dsbA00
pdb bound state: Unbound
  compound: ADP-ribose
  pdb: 2dsbB00
pdb bound state: Unbound
  compound: ADP-ribose
  pdb: 2dsbC00
pdb bound state: Unbound
  compound: ADP-ribose
  pdb: 2dsbD00
pdb bound state: Unbound
  compound: ADP-ribose
  pdb: 2dsdA00
pdb bound state: Unbound
  compound: ADP-ribose
  pdb: 2dsdB00
pdb bound state: Unbound
  compound: ADP-ribose
  pdb: 3ac9A00
pdb bound state: Unbound
  compound: ADP-ribose
  pdb: 3ac9B00
pdb bound state: Unbound
  compound: ADP-ribose
  pdb: 3acaA00
pdb bound state: Unbound
  compound: ADP-ribose
  pdb: 3acaB00
pdb bound state: Analogue
  compound: ADP-ribose
  pdb: 3bm4A00
  ligand het code: ADV
pdb bound state: Analogue
  compound: ADP-ribose
  pdb: 3bm4B00
  ligand het code: ADV
pdb bound state: Unbound
  compound: ADP-ribose
  pdb: 3l85A00
pdb bound state: Unbound
  compound: ADP-ribose
  pdb: 3l85B00
pdb bound state: Unbound
  compound: 8-Oxo-dGDP
  pdb: 2dsbA00
pdb bound state: Unbound
  compound: 8-Oxo-dGDP
  pdb: 2dsbB00
pdb bound state: Unbound
  compound: 8-Oxo-dGDP
  pdb: 2dsbC00
pdb bound state: Unbound
  compound: 8-Oxo-dGDP
  pdb: 2dsbD00
pdb bound state: Unbound
  compound: 8-Oxo-dGDP
  pdb: 2dscA00
pdb bound state: Unbound
  compound: 8-Oxo-dGDP
  pdb: 2dscB00
pdb bound state: Unbound
  compound: 8-Oxo-dGDP
  pdb: 2dsdA00
pdb bound state: Unbound
  compound: 8-Oxo-dGDP
  pdb: 2dsdB00
pdb bound state: Analogue
  compound: 8-Oxo-dGDP
  pdb: 3ac9A00
  ligand het code: 8GD
pdb bound state: Analogue
  compound: 8-Oxo-dGDP
  pdb: 3acaA00
  ligand het code: 8DD
pdb bound state: Analogue
  compound: 8-Oxo-dGDP
  pdb: 3acaB00
  ligand het code: 8DD
pdb bound state: Unbound
  compound: 8-Oxo-dGDP
  pdb: 3bm4A00
pdb bound state: Unbound
  compound: 8-Oxo-dGDP
  pdb: 3bm4B00
pdb bound state: Unbound
  compound: 8-Oxo-dGDP
  pdb: 3l85A00
active site residues resources: Structural basis for different substrate specificities of two ADP-ribose pyrophosphatases from Thermus thermophilus HB8.
active site residues resources: Diverse substrate recognition and hydrolysis mechanisms of human NUDT5.
active site residues resources: http://ezcatdb.cbrc.jp/EzCatDB/reference/S00924#12
references: The structure of ADP-ribose pyrophosphatase reveals the structural basis for the versatility of the Nudix family.
references: Mechanism of the Escherichia coli ADP-ribose pyrophosphatase, a Nudix hydrolase.
references: The crystal structure and mutational analysis of human NUDT9.
references: Structure and mechanism of MT-ADPRase, a nudix hydrolase from Mycobacterium tuberculosis.
references: Structural insights into the Thermus thermophilus ADP-ribose pyrophosphatase mechanism via crystal structures with the bound substrate and metal.
references: Structures and mechanisms of Nudix hydrolases.
references: Molecular mechanism of the Thermus thermophilus ADP-ribose pyrophosphatase from mutational and kinetic studies.
references: Crystal structures of human NUDT5 reveal insights into the structural basis of the substrate specificity.
references: Structural basis for different substrate specificities of two ADP-ribose pyrophosphatases from Thermus thermophilus HB8.
references: Molecular mechanism of ADP-ribose hydrolysis by human NUDT5 from structural and kinetic studies.
references: Diverse substrate recognition and hydrolysis mechanisms of human NUDT5.
comment: This enzyme belongs to Nudix (nucleoside diphosphate linked to x) hydrolase family. There are several types of ADP-ribose pyrophosphatases from various organisms (EzCatDB; S00814, S00921, S00922, S00923, D00880), in terms of substrate specificities, metal binding, active sites and reaction mechanisms. This enzyme also hydrolyzes 8-oxo-dGDP as well as ADP-ribose (see [11]). The magnesium numbering is based on the literature [8], in contrast to those homologous enzymes (EzCatDB; S00814, S00921, S00922), whose numberings are opposite, based on literature [6]. Magnesium-3 is bound to Glu112 and alpha-phosphate of ADP-ribose, whereas Magnesium-2 is bound to Glu112, Glu116, Glu166 and alpha-phosphate. Magnesium-1 is bound to mainchain carbonyl of Ala96, Glu116 and both of the phosphate groups. The water that is bound to magnesium-2 and magnesium-3 is the nucleophile, which attacks on the alpha-phosphate of ADP-ribose(see [10]). On the other hand, for the hydrolysis of 8-oxo-dGDP, the beta-phosphate is attacked by the activated water (see [11]). According to the literature [11], 8-oxo-dGDP adopts a Z-shaped conformation, whereas ADP-ribose adopts a horse-shoe conformation. The difference in the adopted conformations of the substrates leads to the different nucleophilic substitution sites (see [11]). According to the literature [6] and [9], the reaction for ADP-ribose proceeds as follows: (0) A water molecule is bound to Magnesium-2 and -3. These magnesium ions may lower the pKa of the water molecule so that the water molecule can be a better nucleophile, and also stabilize the negative charge on the alpha-phosphate group. On the other hand, magnesium-1 that bridges the two phosphate groups may stabilize the negative charge of the leaving group, beta-phosphate. (1) Glu166 may act as a weak base to deprotonate the water molecule, forming a hydroxide ion. (The contribution of this general base is smaller than those acidic residues, Glu112 and Glu116, which bind magnesium-2 an…

Nucleoside Triphosphate Pyrophosphohydrolase
type: Cath
references: http://www.cathdb.info/version/latest/superfamily/3.90.79.10
catalytic domain: index.html

Purine metabolism
type: KeggPathway
references: KEGG:MAP00230
ec: https://purl.uniprot.org/enzyme/3.6.1.13

Magnesium
type: KeggCofactor
references: KEGG:C00305
ec: https://purl.uniprot.org/enzyme/3.6.1.13
ec: https://purl.uniprot.org/enzyme/3.6.1.58
compound type: divalent metal (Ca2+, Mg2+)
references: CHEBI:18420
references: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi

ADP-ribose
type: KeggSubstrate
references: KEGG:C00301
ec: https://purl.uniprot.org/enzyme/3.6.1.13
compound type: amine group
compound type: carbohydrate
compound type: nucleotide
references: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi

8-Oxo-dGDP
type: KeggSubstrate
references: KEGG:C20176
ec: https://purl.uniprot.org/enzyme/3.6.1.58
compound type: amide group
compound type: amine group
compound type: nucleotide
references: CHEBI:63728
references: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi

H2O
type: KeggSubstrate
references: KEGG:C00001
ec: https://purl.uniprot.org/enzyme/3.6.1.13
ec: https://purl.uniprot.org/enzyme/3.6.1.58
compound type: H2O
references: CHEBI:15377
references: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi

AMP
type: KeggProduct
references: KEGG:C00020
ec: https://purl.uniprot.org/enzyme/3.6.1.13
compound type: amine group
compound type: nucleotide
references: CHEBI:16027
references: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi

D-ribose 5-phosphate
type: KeggProduct
references: KEGG:C00117
ec: https://purl.uniprot.org/enzyme/3.6.1.13
compound type: carbohydrate
compound type: phosphate group/phosphate ion
references: CHEBI:52742
references: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi

8-Oxo-dGMP
type: KeggProduct
references: KEGG:C19968
ec: https://purl.uniprot.org/enzyme/3.6.1.58
compound type: amide group
compound type: amine group
compound type: nucleotide
references: CHEBI:63223
references: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi

Orthophosphate
type: KeggProduct
references: KEGG:C00009
ec: https://purl.uniprot.org/enzyme/3.6.1.58
compound type: phosphate group/phosphate ion
references: CHEBI:26078
references: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi

2dsbA00
type: Pdb
references: 2dsb
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:2dsb
catalytic residue: ARG 84;GLU 166
cofactor binding residue: ALA 96(Magnesium-1);GLU 112(Magnesium-2 & 3);GLU 116(Magnesium-1 & 2);GLU 166(Magnesium-2)

2dsbB00
type: Pdb
references: 2dsb
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:2dsb
catalytic residue: ARG 84;GLU 166
cofactor binding residue: ALA 96(Magnesium-1);GLU 112(Magnesium-2 & 3);GLU 116(Magnesium-1 & 2);GLU 166(Magnesium-2)

2dsbC00
type: Pdb
references: 2dsb
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:2dsb
catalytic residue: ARG 84;GLU 166
cofactor binding residue: ALA 96(Magnesium-1);GLU 112(Magnesium-2 & 3);GLU 116(Magnesium-1 & 2);GLU 166(Magnesium-2)

2dsbD00
type: Pdb
references: 2dsb
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:2dsb
catalytic residue: ARG 84;GLU 166
cofactor binding residue: ALA 96(Magnesium-1);GLU 112(Magnesium-2 & 3);GLU 116(Magnesium-1 & 2);GLU 166(Magnesium-2)

2dscA00
type: Pdb
references: 2dsc
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:2dsc
catalytic residue: ARG 84;GLU 166
cofactor binding residue: ALA 96(Magnesium-1);GLU 112(Magnesium-2 & 3);GLU 116(Magnesium-1 & 2);GLU 166(Magnesium-2)

2dscB00
type: Pdb
references: 2dsc
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:2dsc
catalytic residue: ARG 84;GLU 166
cofactor binding residue: ALA 96(Magnesium-1);GLU 112(Magnesium-2 & 3);GLU 116(Magnesium-1 & 2);GLU 166(Magnesium-2)

2dsdA00
type: Pdb
references: 2dsd
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:2dsd
catalytic residue: ARG 84;GLU 166
cofactor binding residue: ALA 96(Magnesium-1);GLU 112(Magnesium-2 & 3);GLU 116(Magnesium-1 & 2);GLU 166(Magnesium-2)

2dsdB00
type: Pdb
references: 2dsd
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:2dsd
catalytic residue: ARG 84;GLU 166
cofactor binding residue: ALA 96(Magnesium-1);GLU 112(Magnesium-2 & 3);GLU 116(Magnesium-1 & 2);GLU 166(Magnesium-2)

3ac9A00
type: Pdb
references: 3ac9
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:3ac9
catalytic residue: ARG 84;GLU 166
cofactor binding residue: ALA 96(Magnesium-1);GLU 112(Magnesium-2 & 3);GLU 116(Magnesium-1 & 2);GLU 166(Magnesium-2)

3ac9B00
type: Pdb
references: 3ac9
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:3ac9
catalytic residue: ARG 84;GLU 166
cofactor binding residue: ALA 96(Magnesium-1);GLU 112(Magnesium-2 & 3);GLU 116(Magnesium-1 & 2);GLU 166(Magnesium-2)

3acaA00
type: Pdb
references: 3aca
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:3aca
catalytic residue: ARG 84;GLU 166
cofactor binding residue: ALA 96(Magnesium-1);GLU 112(Magnesium-2 & 3);GLU 116(Magnesium-1 & 2);GLU 166(Magnesium-2)

3acaB00
type: Pdb
references: 3aca
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:3aca
catalytic residue: ARG 84;GLU 166
cofactor binding residue: ALA 96(Magnesium-1);GLU 112(Magnesium-2 & 3);GLU 116(Magnesium-1 & 2);GLU 166(Magnesium-2)

3bm4A00
type: Pdb
references: 3bm4
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:3bm4
catalytic residue: ARG 84;GLU 166
cofactor binding residue: ALA 96(Magnesium-1);GLU 112(Magnesium-2 & 3);GLU 116(Magnesium-1 & 2);GLU 166(Magnesium-2)

3bm4B00
type: Pdb
references: 3bm4
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:3bm4
catalytic residue: ARG 84;GLU 166
cofactor binding residue: ALA 96(Magnesium-1);GLU 112(Magnesium-2 & 3);GLU 116(Magnesium-1 & 2);GLU 166(Magnesium-2)

3l85A00
type: Pdb
references: 3l85
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:3l85
catalytic residue: ARG 84;GLU 166
cofactor binding residue: ALA 96(Magnesium-1);GLU 112(Magnesium-2 & 3);GLU 116(Magnesium-1 & 2);GLU 166(Magnesium-2)

3l85B00
type: Pdb
references: 3l85
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:3l85
catalytic residue: ARG 84;GLU 166
cofactor binding residue: ALA 96(Magnesium-1);GLU 112(Magnesium-2 & 3);GLU 116(Magnesium-1 & 2);GLU 166(Magnesium-2)

The structure of ADP-ribose pyrophosphatase reveals the structural basis for the versatility of the Nudix family.
type: BibliographicResource
comment: X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF NATIVE ENZYME, COMPLEX WITH ADP-RIBOSE, COMPLEX WITH GADOLINIUM.
references: http://www.ncbi.nlm.nih.gov/pubmed/11323725
journal: Nat Struct Biol
volume: 8
pages: 467-72
published year: 2001
authors:
  item: Gabelli SB
  item: Bianchet MA
  item: Bessman MJ
  item: Amzel LM
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: Q93K97

Mechanism of the Escherichia coli ADP-ribose pyrophosphatase, a Nudix hydrolase.
type: BibliographicResource
comment: X-RAY CRYSTALLOGRAPHY (2.07 ANGSTROMS), CATALYTIC MECHANISM.
references: http://www.ncbi.nlm.nih.gov/pubmed/12135348
journal: Biochemistry
volume: 41
pages: 9279-85
published year: 2002
authors:
  item: Gabelli SB
  item: Bianchet MA
  item: Ohnishi Y
  item: Ichikawa Y
  item: Bessman MJ
  item: Amzel LM
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: Q93K97

The crystal structure and mutational analysis of human NUDT9.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/12948489
journal: J Mol Biol
volume: 332
pages: 385-98
published year: 2003
authors:
  item: Shen BW
  item: Perraud AL
  item: Scharenberg A
  item: Stoddard BL
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl

Structure and mechanism of MT-ADPRase, a nudix hydrolase from Mycobacterium tuberculosis.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/12906832
journal: Structure
volume: 11
pages: 1015-23
published year: 2003
authors:
  item: Kang LW
  item: Gabelli SB
  item: Cunningham JE
  item: O'Handley SF
  item: Amzel LM
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl

Structural insights into the Thermus thermophilus ADP-ribose pyrophosphatase mechanism via crystal structures with the bound substrate and metal.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/15210687
journal: J Biol Chem
volume: 279
pages: 37163-74
published year: 2004
authors:
  item: Yoshiba S
  item: Ooga T
  item: Nakagawa N
  item: Shibata T
  item: Inoue Y
  item: Yokoyama S
  item: Kuramitsu S
  item: Masui R
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl

Structures and mechanisms of Nudix hydrolases.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/15581572
journal: Arch Biochem Biophys
volume: 433
pages: 129-43
published year: 2005
authors:
  item: Mildvan AS
  item: Xia Z
  item: Azurmendi HF
  item: Saraswat V
  item: Legler PM
  item: Massiah MA
  item: Gabelli SB
  item: Bianchet MA
  item: Kang LW
  item: Amzel LM

Molecular mechanism of the Thermus thermophilus ADP-ribose pyrophosphatase from mutational and kinetic studies.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/15981998
journal: Biochemistry
volume: 44
pages: 9320-9
published year: 2005
authors:
  item: Ooga T
  item: Yoshiba S
  item: Nakagawa N
  item: Kuramitsu S
  item: Masui R

Crystal structures of human NUDT5 reveal insights into the structural basis of the substrate specificity.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/17052728
journal: J Mol Biol
volume: 364
pages: 1021-33
published year: 2006
authors:
  item: Zha M
  item: Zhong C
  item: Peng Y
  item: Hu H
  item: Ding J
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl

Structural basis for different substrate specificities of two ADP-ribose pyrophosphatases from Thermus thermophilus HB8.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/18039767
journal: J Bacteriol
volume: 190
pages: 1108-17
published year: 2008
authors:
  item: Wakamatsu T
  item: Nakagawa N
  item: Kuramitsu S
  item: Masui R

Molecular mechanism of ADP-ribose hydrolysis by human NUDT5 from structural and kinetic studies.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/18462755
journal: J Mol Biol
volume: 379
pages: 568-78
published year: 2008
authors:
  item: Zha M
  item: Guo Q
  item: Zhang Y
  item: Yu B
  item: Ou Y
  item: Zhong C
  item: Ding J
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl

Diverse substrate recognition and hydrolysis mechanisms of human NUDT5.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/21768126
journal: Nucleic Acids Res
volume: 39
pages: 8972-83
published year: 2011
authors:
  item: Arimori T
  item: Tamaoki H
  item: Nakamura T
  item: Kamiya H
  item: Ikemizu S
  item: Takagi Y
  item: Ishibashi T
  item: Harashima H
  item: Sekiguchi M
  item: Yamagata Y
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl

Analogue
compound: Magnesium
pdb: 3ac9B00
ligand het code: 2x_MN

Analogue
compound: Magnesium
pdb: 3acaA00
ligand het code: 3x_MN

Analogue
compound: Magnesium
pdb: 3acaB00
ligand het code: 2x_MN

Analogue
compound: 8-Oxo-dGMP
pdb: 3l85A00
ligand het code: 8OG

ReferenceForCatalyticMechanism
reference index: 2
reference section: FIGURE6

ReferenceForCatalyticMechanism
reference index: 6
reference section: Table1, Fig.5

ReferenceForCatalyticMechanism
reference index: 8

ReferenceForCatalyticMechanism
reference index: 10
reference section: p.571-576, Fig.2

ReferenceForCatalyticMechanism
reference index: 11
reference section: p.8978