DB code: S00814

RLCP classification 1.15.8245.1168 : 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)
3.90.79.10 : Nucleoside Triphosphate Pyrophosphohydrolase S00815 S00920 S00921 S00922 S00923 S00924 S00454

Uniprot Enzyme Name
UniprotKB Protein name Synonyms RefSeq Pfam
Q93K97 ADP-ribose pyrophosphatase
EC 3.6.1.13
ADP-ribose diphosphatase
Adenosine diphosphoribose pyrophosphatase
ADPR-PPase
ADP-ribose phosphohydrolase
ASPPase
NP_417506.1 (Protein)
NC_000913.2 (DNA/RNA sequence)
YP_491226.1 (Protein)
NC_007779.1 (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
Q93K97 ADPP_ECOLI ADP-ribose + H(2)O = AMP + D-ribose 5-phosphate. Homodimer. Binds 3 magnesium ions per subunit.

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
1g0sA00 Unbound Unbound Unbound Unbound
1g0sB00 Unbound Unbound Unbound Unbound
1g9qA00 Unbound Bound:APR Unbound Unbound
1g9qB00 Unbound Bound:APR Unbound Unbound
1ga7A00 Analogue:GD3 Unbound Unbound Unbound
1ga7B00 Analogue:GD3 Unbound Unbound Unbound
1khzA00 Unbound Unbound Unbound Unbound
1khzB00 Bound:3x_MG Analogue:ADV Bound:HOH_407 Unbound Unbound
1viqA00 Unbound Unbound Unbound Unbound
1viqB00 Unbound Unbound Unbound Unbound
1viqC00 Unbound Unbound Unbound Unbound

Reference for Active-site residues
resource references E.C.
literature [2],[6] & Swiss-prot;Q93K97

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
1g0sA00 ARG 79; ALA 96(Magnesium-3);GLU 112(Magnesium-1 & 2);GLU 116(Magnesium-2 & 3);GLU 164(Magnesium-2) invisible 155-162
1g0sB00 ARG 79;GLU 162 ALA 96(Magnesium-3);GLU 112(Magnesium-1 & 2);GLU 116(Magnesium-2 & 3);GLU 164(Magnesium-2)
1g9qA00 ARG 79;GLU 162 ALA 96(Magnesium-3);GLU 112(Magnesium-1 & 2);GLU 116(Magnesium-2 & 3);GLU 164(Magnesium-2) invisible 155-158
1g9qB00 ARG 79;GLU 162 ALA 96(Magnesium-3);GLU 112(Magnesium-1 & 2);GLU 116(Magnesium-2 & 3);GLU 164(Magnesium-2)
1ga7A00 ARG 79;GLU 162 ALA 96(Magnesium-3);GLU 112(Magnesium-1 & 2);GLU 116(Magnesium-2 & 3);GLU 164(Magnesium-2) invisible 155-159
1ga7B00 ARG 79;GLU 162 ALA 96(Magnesium-3);GLU 112(Magnesium-1 & 2);GLU 116(Magnesium-2 & 3);GLU 164(Magnesium-2)
1khzA00 ARG 79;GLU 162 ALA 96(Magnesium-3);GLU 112(Magnesium-1 & 2);GLU 116(Magnesium-2 & 3);GLU 164(Magnesium-2) invisible 155-158
1khzB00 ARG 79;GLU 162 ALA 96(Magnesium-3);GLU 112(Magnesium-1 & 2);GLU 116(Magnesium-2 & 3);GLU 164(Magnesium-2)
1viqA00 ARG 78; ALA 95(Magnesium-3);GLU 111(Magnesium-1 & 2);GLU 115(Magnesium-2 & 3);GLU 163(Magnesium-2) invisible 158-161
1viqB00 ARG 78; ALA 95(Magnesium-3);GLU 111(Magnesium-1 & 2);GLU 115(Magnesium-2 & 3);GLU 163(Magnesium-2) invisible 157-163
1viqC00 ARG 78; ALA 95(Magnesium-3);GLU 111(Magnesium-1 & 2);GLU 115(Magnesium-2 & 3);GLU 163(Magnesium-2) invisible 153-161

References for Catalytic Mechanism
References Sections No. of steps in catalysis
[2]
FIGURE6
[6]
Table1, Fig.5

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 (EzCatDB; S00921, S00922, S00923, S00924, D00880), in terms of substrate specificities, metal binding, active sites and reaction mechanisms.
The magnesium numbering is based on the literature [6]. Magnesium-1 is bound to Glu112 and alpha-phosphate of ADP-ribose, whereas Magnesium-2 is bound to Glu112, Glu116, Glu164 and alpha-phosphate. Magnesium-3 is bound to mainchain carbonyl of Ala96, Glu116 and both of the phosphate groups. The water that is bound to magnesium-1 and magnesium-2 is the nucleophile, which attacks on the alpha-phosphate of ADP-ribose.
According to the literature [2] and [6], the reaction proceeds as follows:
(0) A water molecule is bound to Magnesium-1 and -2. 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-3 that bridges the two phosphate groups may stabilize the negative charge of the leaving group, beta-phosphate.
(1) Glu162 acts as a general 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) Arg79 and magnesium-3 may stabilize the negative charge on the leaving beta-phosphate group.

Created Updated
2009-12-25 2013-03-14