DB code: D00880

RLCP classification 1.15.9995.1169 : Hydrolysis
CATH domain -.-.-.- :
3.90.79.10 : Nucleoside Triphosphate Pyrophosphohydrolase Catalytic domain
E.C. 3.6.1.13
CSA
M-CSA
MACiE

CATH domain Related DB codes (homologues)

Uniprot Enzyme Name
UniprotKB Protein name Synonyms RefSeq Pfam
Q9BW91 ADP-ribose pyrophosphatase, mitochondrial
EC 3.6.1.13
ADP-ribose diphosphatase
ADP-ribose phosphohydrolase
Adenosine diphosphoribose pyrophosphatase
ADPR-PPase
Nucleoside diphosphate-linked moiety X motif 9
Nudix motif 9
NP_001234940.1 (Protein)
NM_001248011.1 (DNA/RNA sequence)
NP_076952.1 (Protein)
NM_024047.4 (DNA/RNA sequence)
NP_932155.1 (Protein)
NM_198038.2 (DNA/RNA sequence)
PF00293 (NUDIX)
[Graphical View]

KEGG enzyme name
ADP-ribose diphosphatase
ADPribose pyrophosphatase
Adenosine diphosphoribose pyrophosphatase
ADPR-PPase

UniprotKB: Accession Number Entry name Activity Subunit Subcellular location Cofactor
Q9BW91 NUDT9_HUMAN ADP-D-ribose + H(2)O = AMP + D-ribose 5-phosphate. Monomer. Interacts with C17orf25. Isoform 1: Mitochondrion. Magnesium. Manganese.

KEGG Pathways
Map code Pathways E.C.
MAP00230 Purine metabolism

Compound table
Cofactors Substrates Products Intermediates
KEGG-id C00305 C00301 C00001 C00020 C00117
E.C.
Compound Magnesium ADP-ribose H2O AMP D-ribose 5-phosphate
Type divalent metal (Ca2+, Mg2+) amine group,carbohydrate,nucleotide H2O amine group,nucleotide carbohydrate,phosphate group/phosphate ion
ChEBI 18420
15377
16027
52742
PubChem 888
445794
22247451
962
6083
439167
1q33A01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound
1qvjA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound
1q33A02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Analogue:BGC
1qvjA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:2x_MG Unbound Unbound Bound:R5P

Reference for Active-site residues
resource references E.C.
literature [2],[3]

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
1q33A01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1qvjA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1q33A02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ARG 204;ARG 273;ASP 305 GLY 214(Magnesium-2);GLU 230(Magnesium-1)
1qvjA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ARG 204;ARG 273;ASP 305 GLY 214(Magnesium-2);GLU 230(Magnesium-1)

References for Catalytic Mechanism
References Sections No. of steps in catalysis
[2]
Figure 6
[3]
p.391-395

References
[1]
Resource
Comments X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF NATIVE ENZYME, COMPLEX WITH ADP-RIBOSE, COMPLEX WITH GADOLINIUM.
Medline ID
PubMed ID 11323725
Journal Nat Struct Biol
Year 2001
Volume 8
Pages 467-72
Authors Gabelli SB, Bianchet MA, Bessman MJ, Amzel LM
Title The structure of ADP-ribose pyrophosphatase reveals the structural basis for the versatility of the Nudix family.
Related PDB 1g0s 1g9q 1ga7
Related UniProtKB Q93K97
[2]
Resource
Comments X-RAY CRYSTALLOGRAPHY (2.07 ANGSTROMS), CATALYTIC MECHANISM.
Medline ID
PubMed ID 12135348
Journal Biochemistry
Year 2002
Volume 41
Pages 9279-85
Authors Gabelli SB, Bianchet MA, Ohnishi Y, Ichikawa Y, Bessman MJ, Amzel LM
Title Mechanism of the Escherichia coli ADP-ribose pyrophosphatase, a Nudix hydrolase.
Related PDB 1khz
Related UniProtKB Q93K97
[3]
Resource
Comments
Medline ID
PubMed ID 12948489
Journal J Mol Biol
Year 2003
Volume 332
Pages 385-98
Authors Shen BW, Perraud AL, Scharenberg A, Stoddard BL
Title The crystal structure and mutational analysis of human NUDT9.
Related PDB 1q33 1qvj
Related UniProtKB
[4]
Resource
Comments
Medline ID
PubMed ID 12906832
Journal Structure
Year 2003
Volume 11
Pages 1015-23
Authors Kang LW, Gabelli SB, Cunningham JE, O'Handley SF, Amzel LM
Title Structure and mechanism of MT-ADPRase, a nudix hydrolase from Mycobacterium tuberculosis.
Related PDB 1mk1 1mp2 1mqe 1mqw 1mr2
Related UniProtKB
[5]
Resource
Comments
Medline ID
PubMed ID 15210687
Journal J Biol Chem
Year 2004
Volume 279
Pages 37163-74
Authors Yoshiba S, Ooga T, Nakagawa N, Shibata T, Inoue Y, Yokoyama S, Kuramitsu S, Masui R
Title Structural insights into the Thermus thermophilus ADP-ribose pyrophosphatase mechanism via crystal structures with the bound substrate and metal.
Related PDB 1v8i 1v8l 1v8m 1v8n 1v8r 1v8s 1v8t 1v8u 1v8v 1v8w 1v8y
Related UniProtKB
[6]
Resource
Comments
Medline ID
PubMed ID 15581572
Journal Arch Biochem Biophys
Year 2005
Volume 433
Pages 129-43
Authors Mildvan AS, Xia Z, Azurmendi HF, Saraswat V, Legler PM, Massiah MA, Gabelli SB, Bianchet MA, Kang LW, Amzel LM
Title Structures and mechanisms of Nudix hydrolases.
Related PDB
Related UniProtKB
[7]
Resource
Comments
Medline ID
PubMed ID 15981998
Journal Biochemistry
Year 2005
Volume 44
Pages 9320-9
Authors Ooga T, Yoshiba S, Nakagawa N, Kuramitsu S, Masui R
Title Molecular mechanism of the Thermus thermophilus ADP-ribose pyrophosphatase from mutational and kinetic studies.
Related PDB
Related UniProtKB
[8]
Resource
Comments
Medline ID
PubMed ID 17052728
Journal J Mol Biol
Year 2006
Volume 364
Pages 1021-33
Authors Zha M, Zhong C, Peng Y, Hu H, Ding J
Title Crystal structures of human NUDT5 reveal insights into the structural basis of the substrate specificity.
Related PDB 2dsb 2dsc 2dsd
Related UniProtKB
[9]
Resource
Comments
Medline ID
PubMed ID 18039767
Journal J Bacteriol
Year 2008
Volume 190
Pages 1108-17
Authors Wakamatsu T, Nakagawa N, Kuramitsu S, Masui R
Title Structural basis for different substrate specificities of two ADP-ribose pyrophosphatases from Thermus thermophilus HB8.
Related PDB
Related UniProtKB
[10]
Resource
Comments
Medline ID
PubMed ID 18462755
Journal J Mol Biol
Year 2008
Volume 379
Pages 568-78
Authors Zha M, Guo Q, Zhang Y, Yu B, Ou Y, Zhong C, Ding J
Title Molecular mechanism of ADP-ribose hydrolysis by human NUDT5 from structural and kinetic studies.
Related PDB 3bm4
Related UniProtKB
[11]
Resource
Comments
Medline ID
PubMed ID 21768126
Journal Nucleic Acids Res
Year 2011
Volume 39
Pages 8972-83
Authors Arimori T, Tamaoki H, Nakamura T, Kamiya H, Ikemizu S, Takagi Y, Ishibashi T, Harashima H, Sekiguchi M, Yamagata Y
Title Diverse substrate recognition and hydrolysis mechanisms of human NUDT5.
Related PDB 3ac9 3aca 3l85
Related UniProtKB

Comments
This enzyme belongs to Nudix (nucleoside diphosphate linked to x) hydrolase family.
There are several types of ADP-ribose pyrophosphatases from various organisms (S00814, S00921, S00922, S00923, S00924, D00880 in EzCatDB), in terms of substrate specificities, metal binding, active-sites and reaction mechanisms. Among these homologous enzymes, the homologue from E. coli (S00814 in EzCatDB) is the closest one (see [3]).
Although Asp305 is at the same position of Glu162, which acts as a general base to activate the hydrolytic water, from E.coli homologous enzyme (S00814), mutant of Asp305 does not reduce the catalytic activity drastically, indicating that this residue may not be a general base (see [3]). Asp305 may participate in orientation of one or two metal ions and the hydrolytic water that is bound to the metal ions (see [3]).
According to the literature [2] and [3], the reaction may proceed as follows:

Created Updated
2009-12-25 2016-07-14