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ATP + beta-D-ribosylnicotinamide
ADP + nicotinamide beta-D-ribonucleotide
ATP + beta-D-ribosylnicotinate
ADP + nicotinate beta-D-ribonucleotide
ATP + cytidine
ADP + CMP
low activity with Nrk1
-
-
?
ATP + nicotinamide mononucleotide
ADP + nicotinamide mononucleotide phosphate
ATP + uridine
ADP + UMP
low activity with Nrk1
-
-
?
GTP + beta-D-ribosylnicotinate
GDP + nicotinate beta-D-ribonucleotide
nicotinic acid riboside is a specific substrate of human Nrk enzymes
-
-
?
ATP + beta-D-ribosylnicotinamide
ADP + nicotinamide beta-D-ribonucleotide
beta-D-ribosylnicotinamide is an NAD+ precursor utilized via the Nrk and Preiss-Hander pathways
-
-
?
ATP + beta-D-ribosylnicotinate
ADP + nicotinate beta-D-ribonucleotide
ATP + cytidine
ADP + CMP
-
-
-
?
ATP + nicotinamide mononucleotide
ADP + nicotinamide mononucleotide phosphate
-
-
-
?
ATP + tiazofurin
ADP + ?
-
-
-
?
ATP + uridine
ADP + UMP
-
-
-
?
GTP + beta-D-ribosylnicotinate
GDP + nicotinate beta-D-ribonucleotide
nicotinic acid riboside is a specific substrate of human Nrk enzymes
-
-
?
additional information
?
-
ATP + beta-D-ribosylnicotinamide
ADP + nicotinamide beta-D-ribonucleotide
-
-
-
?
ATP + beta-D-ribosylnicotinamide
ADP + nicotinamide beta-D-ribonucleotide
beta-D-ribosylnicotinamide is an NAD+ precursor utilized via the Nrk and Preiss-Hander pathways
-
-
?
ATP + beta-D-ribosylnicotinate
ADP + nicotinate beta-D-ribonucleotide
-
-
-
?
ATP + beta-D-ribosylnicotinate
ADP + nicotinate beta-D-ribonucleotide
nicotinic acid riboside is a specific substrate of human Nrk enzymes
-
-
?
ATP + nicotinamide mononucleotide
ADP + nicotinamide mononucleotide phosphate
-
-
-
?
ATP + nicotinamide mononucleotide
ADP + nicotinamide mononucleotide phosphate
binding mode of the substrate, overview
-
-
?
ATP + tiazofurin
ADP + ?
a relatively good Nrk1 substrate
-
-
?
ATP + tiazofurin
ADP + ?
binding mode of the substrate, overview
-
-
?
ATP + beta-D-ribosylnicotinate
ADP + nicotinate beta-D-ribonucleotide
-
-
-
-
?
ATP + beta-D-ribosylnicotinate
ADP + nicotinate beta-D-ribonucleotide
-
-
-
?
ATP + beta-D-ribosylnicotinate
ADP + nicotinate beta-D-ribonucleotide
nicotinic acid riboside is a specific substrate of human Nrk enzymes
-
-
?
additional information
?
-
Asp36 and Glu98 in Nrk1 are essential residues for function in vivo
-
-
?
additional information
?
-
Asp36 and Glu98 in Nrk1 are essential residues for function in vivo
-
-
?
additional information
?
-
ADP binding mode, overview
-
-
?
additional information
?
-
substrate specificity of recombinant Nrk1 and Nrk2, overview. Classification of Nrk1 as an nicotinic acid riboside and tiazofurin:ATP or GTP kinase, Nrk1 displays a 340fold preference for nicotinic acid riboside over cytidine in the KM term and a 500fold preference over either cytidine or uridine in the kcat/KM term. Poor cytidine monophosphate-forming activity of the enzyme. Structural basis of substrate specificity, overview. Base recognition in the Nrk1 nucleoside-binding site excludes uridine but supports beta-D-ribosylnicotinamide phosphorylation
-
-
?
additional information
?
-
substrate specificity of recombinant Nrk1 and Nrk2, overview. Classification of Nrk1 as an nicotinic acid riboside and tiazofurin:ATP or GTP kinase, Nrk1 displays a 340fold preference for nicotinic acid riboside over cytidine in the KM term and a 500fold preference over either cytidine or uridine in the kcat/KM term. Poor cytidine monophosphate-forming activity of the enzyme. Structural basis of substrate specificity, overview. Base recognition in the Nrk1 nucleoside-binding site excludes uridine but supports beta-D-ribosylnicotinamide phosphorylation
-
-
?
additional information
?
-
the main NRK activity in human OVCAR-3 cells is due to the expression of enzyme NRK1
-
-
?
additional information
?
-
Asp35 and Glu100 in Nrk2 are essential residues for function in vivo
-
-
?
additional information
?
-
Asp35 and Glu100 in Nrk2 are essential residues for function in vivo
-
-
?
additional information
?
-
substrate specificity of recombinant Nrk2, overview. Classification of Nrk2 as an ATP-specific nicotinic acid riboside, tiazofurin, and uridine kinase. Poor cytidine monophosphate-forming activity of the enzyme. Structural basis of substrate specificity, overview
-
-
?
additional information
?
-
substrate specificity of recombinant Nrk2, overview. Classification of Nrk2 as an ATP-specific nicotinic acid riboside, tiazofurin, and uridine kinase. Poor cytidine monophosphate-forming activity of the enzyme. Structural basis of substrate specificity, overview
-
-
?
additional information
?
-
-
development of a highly sensitive, rapid and specific coupled enzymatic assay that allows simultaneous determination of NRK activitiy, as well as of nicotinic acid phosphoribosyltransferase, quinolinic acid phosphoribosyltransferase, and nicotinamide phosphoribosyltransferase activities, in various biological samples of various origins, evaluation and optimization using liver extracts, overview
-
-
?
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ATP + beta-D-ribosylnicotinamide
ADP + nicotinamide beta-D-ribonucleotide
-
-
-
?
ATP + beta-D-ribosylnicotinate
ADP + nicotinate beta-D-ribonucleotide
ATP + beta-D-ribosylnicotinate
ADP + nicotinate beta-D-ribonucleotide
additional information
?
-
ATP + beta-D-ribosylnicotinate
ADP + nicotinate beta-D-ribonucleotide
-
-
-
?
ATP + beta-D-ribosylnicotinate
ADP + nicotinate beta-D-ribonucleotide
nicotinic acid riboside is a specific substrate of human Nrk enzymes
-
-
?
ATP + beta-D-ribosylnicotinate
ADP + nicotinate beta-D-ribonucleotide
-
-
-
?
ATP + beta-D-ribosylnicotinate
ADP + nicotinate beta-D-ribonucleotide
nicotinic acid riboside is a specific substrate of human Nrk enzymes
-
-
?
additional information
?
-
Asp36 and Glu98 in Nrk1 are essential residues for function in vivo
-
-
?
additional information
?
-
Asp36 and Glu98 in Nrk1 are essential residues for function in vivo
-
-
?
additional information
?
-
the main NRK activity in human OVCAR-3 cells is due to the expression of enzyme NRK1
-
-
?
additional information
?
-
Asp35 and Glu100 in Nrk2 are essential residues for function in vivo
-
-
?
additional information
?
-
Asp35 and Glu100 in Nrk2 are essential residues for function in vivo
-
-
?
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0.051
beta-D-ribosylnicotinamide
Nrk1, with ATP, pH 7.5, 37°C
0.051 - 0.088
beta-D-ribosylnicotinate
30
cytidine
Nrk1, with ATP, pH 7.5, 37°C
0.27
tiazofurin
Nrk1, with ATP, pH 7.5, 37°C
17
uridine
Nrk1, with ATP, pH 7.5, 37°C
0.063
beta-D-ribosylnicotinamide
Nrk2, with ATP, pH 7.5, 37°C
0.063 - 30
beta-D-ribosylnicotinate
15
cytidine
Nrk2, with ATP, pH 7.5, 37°C
0.11
tiazofurin
Nrk2, with ATP, pH 7.5, 37°C
1.3
uridine
Nrk2, with ATP, pH 7.5, 37°C
0.051
beta-D-ribosylnicotinate
with ATP, pH and temperature not specified in the publication
0.068
beta-D-ribosylnicotinate
Nrk1, with GTP, pH 7.5, 37°C
0.088
beta-D-ribosylnicotinate
Nrk1, with ATP, pH 7.5, 37°C
0.063
beta-D-ribosylnicotinate
with ATP, pH and temperature not specified in the publication
0.19
beta-D-ribosylnicotinate
Nrk2, with ATP, pH 7.5, 37°C
30
beta-D-ribosylnicotinate
Nrk2, with GTP, pH 7.5, 37°C
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0.21
beta-D-ribosylnicotinamide
Nrk1, with ATP, pH 7.5, 37°C
0.21 - 0.6
beta-D-ribosylnicotinate
0.48
cytidine
Nrk1, with ATP, pH 7.5, 37°C
0.35
tiazofurin
Nrk1, with ATP, pH 7.5, 37°C
0.21
uridine
Nrk1, with ATP, pH 7.5, 37°C
0.34
beta-D-ribosylnicotinamide
Nrk2, with ATP, pH 7.5, 37°C
0.34 - 1.7
beta-D-ribosylnicotinate
0.82
cytidine
Nrk2, with ATP, pH 7.5, 37°C
0.49
tiazofurin
Nrk2, with ATP, pH 7.5, 37°C
1.1
uridine
Nrk2, with ATP, pH 7.5, 37°C
0.21
beta-D-ribosylnicotinate
with ATP, pH and temperature not specified in the publication
0.34
beta-D-ribosylnicotinate
Nrk1, with GTP, pH 7.5, 37°C
0.6
beta-D-ribosylnicotinate
Nrk1, with ATP, pH 7.5, 37°C
0.34
beta-D-ribosylnicotinate
with ATP, pH and temperature not specified in the publication
0.75
beta-D-ribosylnicotinate
Nrk2, with ATP, pH 7.5, 37°C
1.7
beta-D-ribosylnicotinate
Nrk2, with GTP, pH 7.5, 37°C
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4.1
beta-D-ribosylnicotinamide
Nrk1, with ATP, pH 7.5, 37°C
4.12 - 6.8
beta-D-ribosylnicotinate
0.016
cytidine
Nrk1, with ATP, pH 7.5, 37°C
1.3
tiazofurin
Nrk1, with ATP, pH 7.5, 37°C
0.012
uridine
Nrk1, with ATP, pH 7.5, 37°C
5.4
beta-D-ribosylnicotinamide
Nrk2, with ATP, pH 7.5, 37°C
0.057 - 5.4
beta-D-ribosylnicotinate
0.055
cytidine
Nrk2, with ATP, pH 7.5, 37°C
4.5
tiazofurin
Nrk2, with ATP, pH 7.5, 37°C
0.85
uridine
Nrk2, with ATP, pH 7.5, 37°C
4.12
beta-D-ribosylnicotinate
with ATP, pH and temperature not specified in the publication
5
beta-D-ribosylnicotinate
Nrk1, with GTP, pH 7.5, 37°C
6.8
beta-D-ribosylnicotinate
Nrk1, with ATP, pH 7.5, 37°C
0.057
beta-D-ribosylnicotinate
Nrk2, with GTP, pH 7.5, 37°C
3.9
beta-D-ribosylnicotinate
Nrk2, with ATP, pH 7.5, 37°C
5.4
beta-D-ribosylnicotinate
with ATP, pH and temperature not specified in the publication
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evolution
the enzyme is structurally similar to Rossmann fold metabolite kinases
malfunction
in NRK1-silenced cells, both nicotinamide riboside- and NMN-mediated rescue from FK866-induced NAD+ depletion and cell death are potently and significantly reduced, overview
evolution
the enzyme is structurally similar to Rossmann fold metabolite kinases
metabolism
the enzyme is involved in the eukaryotic nicotinamide riboside kinase, Nrk, pathway, which is induced in response to nerve damage and promotes replicative life span in yeast, converts nicotinamide riboside to NAD+ by phosphorylation and adenylylation, overview. Nicotinic acid riboside is utilized in vivo by Urh1, Pnp1, and Preiss-Handler salvage
metabolism
the enzyme is involved in the NAD+ biosynthesis pathway. In the initial step of the pathway, NRK activity catalyses the phosphorylation of nicotinamide riboside (NR) to nicotinamide mononucleotide (NMN), see for EC 2.7.1.22. Importance of different salvage pathways involved in metabolising the vitamin B3 class of NAD+ precursor molecules, with a particular focus on the nicotinamide riboside kinase pathway at both a tissue-specific and systemic level, regulation of the NRK enzymes, overview. Alternatively, NRK activity can phosphorylate nicotinic acid riboside (NaR) to nicotinic acid mononucleotide (NaMN)
physiological function
nicotinamide riboside kinase has an important role in the biosynthesis of NAD+ as well as the activation of tiazofurin and other nicotinamide riboside analogues for anticancer therapy
physiological function
NRK2 appears to play a redundant role in NAD+ biosynthesis along with NRK1, at least in unchallenged models, its highly regulated expression particularly in times of stress suggest it may have role beyond NAD+ metabolism
metabolism
the enzyme is involved in the eukaryotic nicotinamide riboside kinase, Nrk, pathway, which is induced in response to nerve damage and promotes replicative life span in yeast, converts nicotinamide riboside to NAD+ by phosphorylation and adenylylation, overview. Nicotinic acid riboside is utilized in vivo by Urh1, Pnp1, and Preiss-Handler salvage
metabolism
-
distinct metabolic routes, starting from various precursors, are known to support NAD+ biosynthesis with tissue/cell-specific efficiencies, probably reflecting differential expression of the corresponding rate-limiting enzymes, i.e. nicotinamide phosphoribosyltransferase, quinolinate phosphoribosyltransferase, nicotinate phosphoribosyltransferase and nicotinamide riboside kinase
metabolism
the enzyme is involved in the NAD+ biosynthesis pathway. In the initial step of the pathway, NRK activity catalyses the phosphorylation of nicotinamide riboside (NR) to nicotinamide mononucleotide (NMN), see for EC 2.7.1.22. Importance of different salvage pathways involved in metabolising the vitamin B3 class of NAD+ precursor molecules, with a particular focus on the nicotinamide riboside kinase pathway at both a tissue-specific and systemic level, regulation of the NRK enzymes, overview. Alternatively, NRK activity can phosphorylate nicotinic acid riboside (NaR) to nicotinic acid mononucleotide (NaMN)
physiological function
-
nicotinamide riboside is a relevant NAD+ precursor
physiological function
NRK2 appears to play a redundant role in NAD+ biosynthesis along with NRK1, at least in unchallenged models, its highly regulated expression particularly in times of stress suggest it may have role beyond NAD+ metabolism
additional information
proposed NRK expression in disease and potential therapeutic interventions
additional information
proposed NRK expression in disease and potential therapeutic interventions
additional information
proposed NRK expression in disease and potential therapeutic interventions
additional information
proposed NRK expression in disease and potential therapeutic interventions
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Nrk1 bound to nucleoside and nucleotide substrates and products, i.e. nicotinamide mononucleotide, ADP, tiazofurin, beta-D-ribosylnicotinate with AppNHp, and beta-D-ribosylnicotinate alone, addition of 10 mM ligand and 20 mM MgCl2, overview. Usage of different crystallization solutions depending on the ligand, containing PEG 2000 mono-methylether or PEG 3350 or PEG 4000 at 15-35%, at pH 5.0-8.0, with 0.2 M NaH2PO4, and different buffers, X-ray diffraction structure determination and analysis at 1.32-1.95 A resolution, molecular replacement
NRK1 in complex with the reaction product nicotinamide mononucleotide, and NRK1 in a ternary complex with ADP and the anticancer drug tiazofurin, sitting-drop vapor-diffusion method, 22°C, mixing of protein solution containing 20 mg/ml protein, 2 mM ligand, 20 mM Tris, pH 7.5-7.8, 200 mM NaCl, 5 mM DTT, with reservoir solution containing 28% w/v PEG 3350, 200 mM NH4Cl, 5 mM DTT, and 5 mM Na2HPO4, X-ray diffraction structure determination and analysis at 1.5 A and 2.7 A resolution, respectively, modeling
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Khan, J.A.; Xiang, S.; Tong, L.
Crystal structure of human nicotinamide riboside kinase
Structure
15
1005-1013
2007
Homo sapiens (Q9NWW6)
brenda
Tempel, W.; Rabeh, W.M.; Bogan, K.L.; Belenky, P.; Wojcik, M.; Seidle, H.F.; Nedyalkova, L.; Yang, T.; Sauve, A.A.; Park, H.W.; Brenner, C.
Nicotinamide riboside kinase structures reveal new pathways to NAD+
PLoS Biol.
5
e263
2007
Homo sapiens (Q9NPI5), Homo sapiens (Q9NWW6)
brenda
Zamporlini, F.; Ruggieri, S.; Mazzola, F.; Amici, A.; Orsomando, G.; Raffaelli, N.
Novel assay for simultaneous measurement of pyridine mononucleotides synthesizing activities allows dissection of the NAD+ biosynthetic machinery in mammalian cells
FEBS J.
281
5104-5119
2014
Homo sapiens
brenda
Sociali, G.; Raffaghello, L.; Magnone, M.; Zamporlini, F.; Emionite, E.; Sturla, L.; Bianchi, G.; Vigliarolo, T.; Nahimana, A.; Nencioni, A.; Raffaelli, N.; Bruzzone, S
Antitumor effect of combined NAMPT and CD73 inhibition in an ovarian cancer model
Oncotarget
7
2968-2984
2016
Homo sapiens (Q9NWW6)
brenda
Fletcher, R.S.; Lavery, G.G.
The emergence of the nicotinamide riboside kinases in the regulation of NAD+ metabolism
J. Mol. Endocrinol.
61
R107-R121
2018
Homo sapiens (Q9NPI5), Homo sapiens (Q9NWW6)
brenda