S00922
type: Enzyme
rlcp: p1169
cath: Nucleoside Triphosphate Pyrophosphohydrolase
ec: https://purl.uniprot.org/enzyme/3.6.1.13
uniprot: Q84CU3
kegg enzyme: ADP-ribose diphosphatase
kegg enzyme: ADPribose pyrophosphatase
kegg enzyme: Adenosine diphosphoribose pyrophosphatase
kegg enzyme: ADPR-PPase
kegg pathway: Purine metabolism
kegg cofactor: Magnesium
kegg substrate: ADP-ribose
kegg substrate: H2O
kegg product: AMP
kegg product: D-ribose 5-phosphate
pdb: 1v8iA00
pdb: 1v8lA00
pdb: 1v8mA00
pdb: 1v8nA00
pdb: 1v8rA00
pdb: 1v8sA00
pdb: 1v8tA00
pdb: 1v8uA00
pdb: 1v8vA00
pdb: 1v8wA00
pdb: 1v8yA00
pdb bound state: Unbound
  compound: ADP-ribose
  pdb: 1v8iA00
pdb bound state: Unbound
  compound: ADP-ribose
  pdb: 1v8nA00
pdb bound state: Unbound
  compound: ADP-ribose
  pdb: 1v8sA00
pdb bound state: Unbound
  compound: ADP-ribose
  pdb: 1v8tA00
pdb bound state: Unbound
  compound: ADP-ribose
  pdb: 1v8uA00
pdb bound state: Unbound
  compound: ADP-ribose
  pdb: 1v8wA00
pdb bound state: Unbound
  compound: ADP-ribose
  pdb: 1v8yA00
pdb bound state: Unbound
  compound: Magnesium
  pdb: 1v8iA00
pdb bound state: Unbound
  compound: Magnesium
  pdb: 1v8lA00
pdb bound state: Analogue
  compound: Magnesium
  pdb: 1v8mA00
  ligand het code: 2x_GD
pdb bound state: Analogue
  compound: Magnesium
  pdb: 1v8nA00
  ligand het code: _ZN
pdb bound state: Analogue
  compound: Magnesium
  pdb: 1v8rA00
  ligand het code: _ZN
pdb bound state: Analogue
  compound: Magnesium
  pdb: 1v8tA00
  ligand het code: _ZN
pdb bound state: Unbound
  compound: Magnesium
  pdb: 1v8wA00
pdb bound state: Analogue
  compound: Magnesium
  pdb: 1v8yA00
  ligand het code: _ZN
pdb bound state: Unbound
  compound: AMP
  pdb: 1v8iA00
pdb bound state: Unbound
  compound: AMP
  pdb: 1v8lA00
pdb bound state: Unbound
  compound: AMP
  pdb: 1v8mA00
pdb bound state: Unbound
  compound: AMP
  pdb: 1v8nA00
pdb bound state: Unbound
  compound: AMP
  pdb: 1v8rA00
pdb bound state: Unbound
  compound: AMP
  pdb: 1v8tA00
pdb bound state: Unbound
  compound: AMP
  pdb: 1v8uA00
pdb bound state: Unbound
  compound: AMP
  pdb: 1v8vA00
pdb bound state: Unbound
  compound: AMP
  pdb: 1v8wA00
pdb bound state: Analogue
  compound: AMP
  pdb: 1v8yA00
  ligand het code: APR
pdb bound state: Unbound
  compound: D-ribose 5-phosphate
  pdb: 1v8iA00
pdb bound state: Unbound
  compound: D-ribose 5-phosphate
  pdb: 1v8lA00
pdb bound state: Unbound
  compound: D-ribose 5-phosphate
  pdb: 1v8mA00
pdb bound state: Unbound
  compound: D-ribose 5-phosphate
  pdb: 1v8nA00
pdb bound state: Unbound
  compound: D-ribose 5-phosphate
  pdb: 1v8rA00
pdb bound state: Unbound
  compound: D-ribose 5-phosphate
  pdb: 1v8sA00
pdb bound state: Analogue
  compound: D-ribose 5-phosphate
  pdb: 1v8tA00
  ligand het code: R5P
pdb bound state: Unbound
  compound: D-ribose 5-phosphate
  pdb: 1v8uA00
pdb bound state: Unbound
  compound: D-ribose 5-phosphate
  pdb: 1v8vA00
pdb bound state: Unbound
  compound: D-ribose 5-phosphate
  pdb: 1v8wA00
pdb bound state: Unbound
  compound: D-ribose 5-phosphate
  pdb: 1v8yA00
active site residues resources: Structures and mechanisms of Nudix hydrolases.
active site residues resources: Molecular mechanism of the Thermus thermophilus ADP-ribose pyrophosphatase from mutational and kinetic studies.
active site residues resources: Crystal structures of human NUDT5 reveal insights into the structural basis of the substrate specificity.
reference for catalytic mechanism: ReferenceForCatalyticMechanism
  reference index: 2
  reference section: FIGURE6
reference for catalytic mechanism: ReferenceForCatalyticMechanism
  reference index: 5
  reference section: p.37171-37172, Fig.8
reference for catalytic mechanism: ReferenceForCatalyticMechanism
  reference index: 6
  reference section: Table1, Fig.5
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, S00923, S00924, D00880), in terms of substrate specificities, metal binding, active sites and reaction mechanisms. Although other homologous enzymes bind three metal ions, this enzyme binds only two magnesium ions, which corresponds to the magnesium-2 and magnesium-3 in the homologous enzymes. The magnesium numbering is based on the literature [5]. Magnesium-1 is bound to Glu82 and alpha-phosphate of ADP-ribose, whereas Magnesium-2 is bound to mainchain carbonyl of Ala66, Glu86 and both of the phosphate groups. The water that is bound to magnesium-1 is the nucleophile, which attacks on the alpha-phosphate of ADP-ribose. According to the literature [5] and [6], the reaction proceeds as follows: (0) A water molecule is bound to Magnesium-1. The magnesium ion 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-2 that bridges the two phosphate groups may stabilize the negative charge of the leaving group, beta-phosphate. Moreover, Arg81 may modulate the activity of Glu82, which binds the magnesium-1. (1) Glu70 may act as a weak base to deprotonate the water molecule, forming a hydroxide ion. (2) The hydroxide ion makes a nucleophilic attack on the alpha-phosphate of ADP-ribose. (SN2-like reaction) (3) Arg54 and magnesium-2 may stabilize the negative charge on the leaving beta-phosphate group.

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

Magnesium
type: KeggCofactor
references: KEGG:C00305
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
compound type: amine group
compound type: carbohydrate
compound type: nucleotide
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

AMP
type: KeggProduct
references: KEGG:C00020
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
compound type: carbohydrate
compound type: phosphate group/phosphate ion
references: CHEBI:52742
references: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi

1v8iA00
type: Pdb
references: 1v8i
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1v8i
catalytic residue: ARG 54;GLU 70;ARG 81
cofactor binding residue: GLU 82(Magnesium-1);ALA 66;GLU 86(Magnesium-2)
comment: invisible 123-130

1v8lA00
type: Pdb
references: 1v8l
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1v8l
catalytic residue: ARG 54;GLU 70;ARG 81
cofactor binding residue: GLU 82(Magnesium-1);ALA 66;GLU 86(Magnesium-2)
comment: invisible 124-125

1v8mA00
type: Pdb
references: 1v8m
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1v8m
catalytic residue: ARG 54;GLU 70;ARG 81
cofactor binding residue: GLU 82(Magnesium-1);ALA 66;GLU 86(Magnesium-2)

1v8nA00
type: Pdb
references: 1v8n
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1v8n
catalytic residue: ARG 54;GLU 70;ARG 81
cofactor binding residue: GLU 82(Magnesium-1);ALA 66;GLU 86(Magnesium-2)
comment: invisible 123-130

1v8rA00
type: Pdb
references: 1v8r
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1v8r
catalytic residue: ARG 54;GLU 70;ARG 81
cofactor binding residue: GLU 82(Magnesium-1);ALA 66;GLU 86(Magnesium-2)
comment: invisible 124-129

1v8sA00
type: Pdb
references: 1v8s
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1v8s
catalytic residue: ARG 54;GLU 70;ARG 81
cofactor binding residue: GLU 82(Magnesium-1);ALA 66;GLU 86(Magnesium-2)
comment: invisible 123-129

1v8tA00
type: Pdb
references: 1v8t
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1v8t
catalytic residue: ARG 54;GLU 70;ARG 81
cofactor binding residue: GLU 82(Magnesium-1);ALA 66;GLU 86(Magnesium-2)
comment: invisible 124-129

1v8uA00
type: Pdb
references: 1v8u
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1v8u
catalytic residue: ARG 54;GLU 70;ARG 81
cofactor binding residue: ;ALA 66;GLU 86(Magnesium-2)
comment: mutant E82Q, invisible 124-128

1v8vA00
type: Pdb
references: 1v8v
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1v8v
catalytic residue: ARG 54;GLU 70;ARG 81
cofactor binding residue: GLU 82(Magnesium-1);ALA 66; (Magnesium-2)
comment: mutant E86Q, invisible 124-128

1v8wA00
type: Pdb
references: 1v8w
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1v8w
catalytic residue: ARG 54;GLU 70;ARG 81
cofactor binding residue: ;ALA 66;GLU 86(Magnesium-2)
comment: mutant E82Q, invisible 126-129

1v8yA00
type: Pdb
references: 1v8y
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1v8y
catalytic residue: ARG 54;GLU 70;ARG 81
cofactor binding residue: GLU 82(Magnesium-1);ALA 66; (Magnesium-2)
comment: mutant E86Q, invisible 123-130

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

ReferenceForCatalyticMechanism
reference index: 7
reference section: Figure 6