DB code: D00880

RLCP classification	1.15.9995.1169 : Hydrolysis
CATH domain	-.-.-.- :
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 18420		15377 15377	16027 16027	52742 52742
PubChem	888 888	445794 445794	22247451 962 22247451 962	6083 6083	439167 439167

1q33A01	Unbound	Unbound		Unbound	Unbound
1qvjA01	Unbound	Unbound		Unbound	Unbound
1q33A02	Unbound	Unbound		Unbound	Analogue:BGC
1qvjA02	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
1qvjA01
1q33A02	ARG 204;ARG 273;ASP 305	GLY 214(Magnesium-2);GLU 230(Magnesium-1)
1qvjA02	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:

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