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Information on EC 3.6.1.64 - inosine diphosphate phosphatase
for references in articles please use BRENDA:EC3.6.1.64
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EC Tree 3 Hydrolases
3.6 Acting on acid anhydrides
3.6.1 In phosphorus-containing anhydrides
3.6.1.64 inosine diphosphate phosphatase
IUBMB Comments
The human enzyme also hydrolyses GDP and dGDP, and to a lesser extent ITP, dITP and XTP.
The enzyme appears in viruses and cellular organisms
showSynonyms
(deoxy)inosine diphosphatase, more
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SYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
NUD16
Nudt16
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REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
dIDP + H2O = dIMP + phosphate
-
-
-
-
IDP + H2O = IMP + phosphate
-
-
-
-
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PATHWAY SOURCE
PATHWAYS
KEGG
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SYSTEMATIC NAME
IUBMB Comments
inosine diphosphate phosphatase
The human enzyme also hydrolyses GDP and dGDP, and to a lesser extent ITP, dITP and XTP.
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SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
LITERATURE
COMMENTARY
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
GppG + H2O
2 GMP
Substrates: the hydrolysis rate for GppG is much higher than that of its m7GppG counterpart
Products: -
Products: -
?
m7GppG + H2O
N7-methyl-GMP + GMP
Substrates: the hydrolysis rate for GppG is much higher than that of its m7GppG counterpart
Products: -
Products: -
?
dITP + H2O
dIMP + diphosphate
Substrates: -
Products: hydrolysis of ITP generates IMP but not phosphate
Products: hydrolysis of ITP generates IMP but not phosphate
?
additional information
?
-
Substrates: rate of the catalytic cycle is primarily regulated by the product-release step
Products: -
Products: -
?
additional information
?
-
Substrates: quantitative comparison of the affinity of hNudt16 towards a set of previously published substrates, as well as identification of other potential substrates. IDP, GppG, m7GppG, AppA, dpCoA, and NADH are hydrolyzed by hNudt16 with a strong substrate preference for inosine or guanosine containing compounds. hNudt16 has the highest affinity towards IDP and GppG. Dinucleotides containing adenine, AppA, dpCoA, NAD, and NADH are much less susceptible to enzymatic cleavage by this enzyme. The enzyme also catalyzes the reaction of EC 3.6.1.62, hydrolyzing the canonical 5'-RNA cap structure on a subset of cytoplasmic mRNAs and small nucleolar RNAs, and releasing m7GDP or m3GDP and 5'-monophosphate RNA. No significant difference in hydrolysis is observed when compounds (m7GpppG or GpppG) are bound to the RNA chain, cf. EC 3.6.1.62. No activity with ADPr and m7GDP. Molecular docking of selected ligands to the hNudt16 crystal structure. IDP and GppG strongly interact with enzyme mutant hNudt16E76Q, while AppA shows weaker interactions with hNudt16E76Q
Products: -
Products: -
-
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NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
LITERATURE
COMMENTARY
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
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METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Co2+
essential for substrate hydrolysis, is bound by the Nudix box (loop-helix-loop)
Mg2+
Mn2+
essential for substrate hydrolysis, is bound by the Nudix box (loop-helix-loop)
additional information
Mg2+
2 Mg2+ ions per enzyme molecule, essential for substrate hydrolysis, is bound by the Nudix box (loop-helix-loop). Binding and catalytic structures, overview. Saturation at 20 mM
additional information
-
divalent cation absolutely required. No IDP hydrolysis in the presence of 5mM Mn2+, Co2+ or Ca2+
additional information
divalent cation absolutely required. No IDP hydrolysis in the presence of 5mM Mn2+, Co2+ or Ca2+
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INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
bifunctional U8 snoRNA-decapping enzyme and IDP phosphatase
SwissProt
brenda
bifunctional U8 snoRNA-decapping enzyme and IDP phosphatase
SwissProt
brenda
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SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
additional information
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LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
Highest Expressing Human Cell Lines
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GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
evolution
the human Nudt16 protein (hNudt16) is a member of the NUDIX family of enzymes involved in cellular metabolism, homeostasis, and mRNA processing. As NUDIX refers to a nucleoside diphosphate linked to another moiety X, the enzymes of this family catalyze the hydrolysis of the phosphodiester bond in a broad spectrum of substrates (including nucleoside triphosphates, coenzymes, nucleotide sugars, dinucleoside polyphosphates). hNudt16 orthologues have been identified in numerous eukaryotic species, including vertebrates (e.g. frog, rat, zebra fish, and lamprey) and invertebrates (e.g. earthworms), indicating an evolutionarily conserved biological role
physiological function
additional information
molecular docking of hNudt16-ligand binding inside the hNudt16 pocket reveals two binding modes for representative substrates. Nucleobase stabilization by P stacking interactions with His24 has been associated with strong binding of hNudt16 substrates. The Nudix family of enzymes have a highly conserved Nudix box (GX5EX7REUXEEXGU), where X may be any residue and U represents hydrophobic residues. The structural motif of the Nudix box (loop-helix-loop) acts as a substrate-binding and catalytic site and is also involved in binding of metal ions. Residues E79 and E80 belong to the NUDIX motif and are involved in the coordination of Mg2+ ions in the structure, they play a role in the catalytic mechanism. In dinucleotide ligands, one of the nucleobases fit into the hNudt16 pocket, while the other nucleobase adopted a range of conformations, interacting with various amino acids on the hNudt16 surface, including Gly101, Ser102, Ala4, Ser 166, and His99
physiological function
knockdown in HeLa MR cells causes cell cycle arrest in S-phase, reduces cell proliferation, and leads to increased accumulation of single-strand breaks in nuclear DNA as well as increased levels of inosine in RNA
physiological function
Nudt16 is a member of the NUDIX family of hydrolases that show specificity towards substrates consisting of a nucleoside diphosphate linked to another moiety X. The enzyme has a wide substrate specificity and several biological functions, overview
Show AA Sequence and Transmembrane Helices (735 entries)
Please use the AA Sequence and Transmembrane Helices Search for a specific query.
Please use the AA Sequence and Transmembrane Helices Search for a specific query.
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PDB
SCOP
CATH
UNIPROT
ORGANISM
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SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
dimer
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CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
mutant A22V,structure forms an alpha/beta/alpha sandwich which is constituted by two beta-sheets, one being composed of two parallel beta-strands lined by two anti-parallel beta-strands and the second one by three anti-parallel beta-strands. The protein is decorated with five additional motifs being part of the hydrophobic core or serving roles to stabilize the dimer
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PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
E76Q
hydrolytically inactive mutant, structure comparisons with the wild-type enzyme
E79K/E80K
hydrolytically inactive mutant, structure comparisons with the wild-type enzyme
E79Q/E80Q
hydrolytically inactive mutant, structure comparisons with the wild-type enzyme
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TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
56
enzyme mutant E76Q without Mg2+, in the E76Q mutant, increasing the magnesium concentration gradually increases the melting temperature: Ligands GppG, IDP, m7GppG, GDP, GpppG, IMP, m7GpppG significantly increase the thermal stability of the mutant enzyme, while GMP, dpCoA, NADH, and AppA show a lower effect and CDP, m7GDP, NAD+, and ADPr show only a slight effect. Preesence of dye SYPRO Orange has also only a slight effect
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CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
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REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Iyama, T.; Abolhassani, N.; Tsuchimoto, D.; Nonaka, M.; Nakabeppu, Y.
NUDT16 is a (deoxy)inosine diphosphatase, and its deficiency induces accumulation of single-strand breaks in nuclear DNA and growth arrest
Nucleic Acids Res.
38
4834-4843
2010
Homo sapiens, Homo sapiens (Q96DE0), Mus musculus (Q6P3D0)
brenda
Tresaugues, L.; Lundbaeck, T.; Welin, M.; Flodin, S.; Nyman, T.; Silvander, C.; Graeslund, S.; Nordlund, P.
Structural basis for the specificity of human NUDT16 and its regulation by inosine monophosphate
PLoS ONE
10
e0131507
2015
Homo sapiens (Q96DE0)
brenda
Chrabaszczewska, M.; Winiewska-Szajewska, M.; Ostrowska, N.; Bojarska, E.; Stepinski, J.; Mancewicz, L.; Lukaszewicz, M.; Trylska, J.; Taube, M.; Kozak, M.; Darzynkiewicz, E.; Grzela, R.
Insight into the binding and hydrolytic preferences of hNudt16 based on nucleotide diphosphate substrates
Int. J. Mol. Sci.
22
10929
2021
Homo sapiens (Q96DE0)
brenda
EXTERNAL LINKS (specific for EC-Number 3.6.1.64)
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