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
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
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
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
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
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
in addition to the seven-component pyridine nucleotide cycle, an eight-component cycle involving nicotinate riboside kinase operates in plants. NaR kinase does not make a significant contribution to salvage for pyridine nucleotide synthesis
nicotinamide riboside elevates NAD+ levels via the nicotinamide riboside kinase pathway and by a pathway initiated by splitting the nucleoside into a nicotinamide base followed by nicotinamide salvage. Yeast nicotinic acid riboside utilization largely depends on uridine hydrolase and nicotinamide riboside kinase, and nicotinic acid riboside bioavailability is increased by ester modification
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
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
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)
nicotinamide riboside elevates NAD+ levels via the nicotinamide riboside kinase pathway and by a pathway initiated by splitting the nucleoside into a nicotinamide base followed by nicotinamide salvage. Yeast nicotinic acid riboside utilization largely depends on uridine hydrolase and nicotinamide riboside kinase, and nicotinic acid riboside bioavailability is increased by ester modification
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
nicotinamide riboside kinase increases the NAD+ levels via convertion of the substrate nicotinamide riboside and thereby extending replicative lifespan and increases Sir2-dependent gene silencing
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
nicotinamide riboside kinase increases the NAD+ levels via convertion of the substrate nicotinamide riboside and thereby extending replicative lifespan and increases Sir2-dependent gene silencing
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CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
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
His-tagged wild-type Nrk1 expression in Escherichia coli, expression of wild-type and mutant Nrk1 from the GAL1 promoter on a LEU2 plasmid in Saccharomyces cerevisiae strain BY278
His-tagged wild-type Nrk2 expression in Escherichia coli, expression of wild-type and mutant Nrk2 from the GAL1 promoter on a LEU2 plasmid in Saccharomyces cerevisiae strain BY278
Belenky, P.; Christensen, K.C.; Gazzaniga, F.; Pletnev, A.A.; Brenner, C.
Nicotinamide riboside and nicotinic acid riboside salvage in fungi and mammals. Quantitative basis for Urh1 and purine nucleoside phosphorylase function in NAD+ metabolism
Novel assay for simultaneous measurement of pyridine mononucleotides synthesizing activities allows dissection of the NAD+ biosynthetic machinery in mammalian cells