EzCatDB: D00880
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DB codeD00880
RLCP classification1.15.9995.1169 : Hydrolysis
CATH domainDomain 1-.-.-.-
Domain 23.90.79.10 : Nucleoside Triphosphate PyrophosphohydrolaseCatalytic domain
E.C.3.6.1.13


Enzyme Name
UniProtKBKEGG

Q9BW91
Protein nameADP-ribose pyrophosphatase, mitochondrialADP-ribose diphosphatase
ADPribose pyrophosphatase
Adenosine diphosphoribose pyrophosphatase
ADPR-PPase
SynonymsEC 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
RefSeqNP_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)
PfamPF00293 (NUDIX)
[Graphical view]

KEGG pathways
MAP codePathways
MAP00230Purine metabolism

UniProtKB:Accession NumberQ9BW91
Entry nameNUDT9_HUMAN
ActivityADP-D-ribose + H(2)O = AMP + D-ribose 5-phosphate.
SubunitMonomer. Interacts with C17orf25.
Subcellular locationIsoform 1: Mitochondrion.
CofactorMagnesium.,Manganese.

Compound table: links to PDB-related databases & PoSSuM

CofactorsSubstratesProducts
KEGG-idC00305C00301C00001C00020C00117
CompoundMagnesiumADP-riboseH2OAMPD-ribose 5-phosphate
Typedivalent metal (Ca2+, Mg2+)amine group,carbohydrate,nucleotideH2Oamine group,nucleotidecarbohydrate,phosphate group/phosphate ion
ChEBI18420

15377
16027
52742
PubChem888
445794
22247451
962
6083
439167
             
1q33A01UnboundUnbound UnboundUnbound
1qvjA01UnboundUnbound UnboundUnbound
1q33A02UnboundUnbound UnboundAnalogue:BGC
1qvjA02Bound:2x_MGUnbound UnboundBound:R5P

Active-site residues
resource
literature [2],[3]
pdbCatalytic residuesCofactor-binding residues
          
1q33A01 
 
1qvjA01 
 
1q33A02ARG 204;ARG 273;ASP 305
GLY 214(Magnesium-2);GLU 230(Magnesium-1)
1qvjA02ARG 204;ARG 273;ASP 305
GLY 214(Magnesium-2);GLU 230(Magnesium-1)

References for Catalytic Mechanism
ReferencesSectionsNo. of steps in catalysis
[2]Figure 6
[3]p.391-395

references
[1]
CommentsX-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF NATIVE ENZYME, COMPLEX WITH ADP-RIBOSE, COMPLEX WITH GADOLINIUM.
PubMed ID11323725
JournalNat Struct Biol
Year2001
Volume8
Pages467-72
AuthorsGabelli SB, Bianchet MA, Bessman MJ, Amzel LM
TitleThe structure of ADP-ribose pyrophosphatase reveals the structural basis for the versatility of the Nudix family.
Related PDB1g0s,1g9q,1ga7
Related UniProtKBQ93K97
[2]
CommentsX-RAY CRYSTALLOGRAPHY (2.07 ANGSTROMS), CATALYTIC MECHANISM.
PubMed ID12135348
JournalBiochemistry
Year2002
Volume41
Pages9279-85
AuthorsGabelli SB, Bianchet MA, Ohnishi Y, Ichikawa Y, Bessman MJ, Amzel LM
TitleMechanism of the Escherichia coli ADP-ribose pyrophosphatase, a Nudix hydrolase.
Related PDB1khz
Related UniProtKBQ93K97
[3]
PubMed ID12948489
JournalJ Mol Biol
Year2003
Volume332
Pages385-98
AuthorsShen BW, Perraud AL, Scharenberg A, Stoddard BL
TitleThe crystal structure and mutational analysis of human NUDT9.
Related PDB1q33,1qvj
[4]
PubMed ID12906832
JournalStructure
Year2003
Volume11
Pages1015-23
AuthorsKang LW, Gabelli SB, Cunningham JE, O'Handley SF, Amzel LM
TitleStructure and mechanism of MT-ADPRase, a nudix hydrolase from Mycobacterium tuberculosis.
Related PDB1mk1,1mp2,1mqe,1mqw,1mr2
[5]
PubMed ID15210687
JournalJ Biol Chem
Year2004
Volume279
Pages37163-74
AuthorsYoshiba S, Ooga T, Nakagawa N, Shibata T, Inoue Y, Yokoyama S, Kuramitsu S, Masui R
TitleStructural insights into the Thermus thermophilus ADP-ribose pyrophosphatase mechanism via crystal structures with the bound substrate and metal.
Related PDB1v8i,1v8l,1v8m,1v8n,1v8r,1v8s,1v8t,1v8u,1v8v,1v8w,1v8y
[6]
PubMed ID15581572
JournalArch Biochem Biophys
Year2005
Volume433
Pages129-43
AuthorsMildvan AS, Xia Z, Azurmendi HF, Saraswat V, Legler PM, Massiah MA, Gabelli SB, Bianchet MA, Kang LW, Amzel LM
TitleStructures and mechanisms of Nudix hydrolases.
[7]
PubMed ID15981998
JournalBiochemistry
Year2005
Volume44
Pages9320-9
AuthorsOoga T, Yoshiba S, Nakagawa N, Kuramitsu S, Masui R
TitleMolecular mechanism of the Thermus thermophilus ADP-ribose pyrophosphatase from mutational and kinetic studies.
[8]
PubMed ID17052728
JournalJ Mol Biol
Year2006
Volume364
Pages1021-33
AuthorsZha M, Zhong C, Peng Y, Hu H, Ding J
TitleCrystal structures of human NUDT5 reveal insights into the structural basis of the substrate specificity.
Related PDB2dsb,2dsc,2dsd
[9]
PubMed ID18039767
JournalJ Bacteriol
Year2008
Volume190
Pages1108-17
AuthorsWakamatsu T, Nakagawa N, Kuramitsu S, Masui R
TitleStructural basis for different substrate specificities of two ADP-ribose pyrophosphatases from Thermus thermophilus HB8.
[10]
PubMed ID18462755
JournalJ Mol Biol
Year2008
Volume379
Pages568-78
AuthorsZha M, Guo Q, Zhang Y, Yu B, Ou Y, Zhong C, Ding J
TitleMolecular mechanism of ADP-ribose hydrolysis by human NUDT5 from structural and kinetic studies.
Related PDB3bm4
[11]
PubMed ID21768126
JournalNucleic Acids Res
Year2011
Volume39
Pages8972-83
AuthorsArimori T, Tamaoki H, Nakamura T, Kamiya H, Ikemizu S, Takagi Y, Ishibashi T, Harashima H, Sekiguchi M, Yamagata Y
TitleDiverse substrate recognition and hydrolysis mechanisms of human NUDT5.
Related PDB3ac9,3aca,3l85

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:

createdupdated
2009-12-252016-07-14


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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