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Literature summary for 2.7.1.173 extracted from

  • 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+ (2007), PLoS Biol., 5, e263.
    View publication on PubMedView publication on EuropePMC

Cloned(Commentary)

Cloned (Comment) Organism
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 Homo sapiens
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 Homo sapiens

Crystallization (Commentary)

Crystallization (Comment) Organism
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 Homo sapiens

Protein Variants

Protein Variants Comment Organism
D35A site-directed mutagenesis of Nrk2 Homo sapiens
D36A site-directed mutagenesis of Nrk1 Homo sapiens
E100A site-directed mutagenesis of Nrk2, mutant activity in ATP-dependent phosphorylation is below the level of detection Homo sapiens
E174R site-directed mutagenesis of Nrk2 Homo sapiens
E98A site-directed mutagenesis of Nrk1, mutant activity in ATP-dependent phosphorylation is below the level of detection Homo sapiens

KM Value [mM]

KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
0.051
-
beta-D-ribosylnicotinamide Nrk1, with ATP, pH 7.5, 37°C Homo sapiens
0.063
-
beta-D-ribosylnicotinamide Nrk2, with ATP, pH 7.5, 37°C Homo sapiens
0.068
-
beta-D-ribosylnicotinate Nrk1, with GTP, pH 7.5, 37°C Homo sapiens
0.088
-
beta-D-ribosylnicotinate Nrk1, with ATP, pH 7.5, 37°C Homo sapiens
0.11
-
tiazofurin Nrk2, with ATP, pH 7.5, 37°C Homo sapiens
0.19
-
beta-D-ribosylnicotinate Nrk2, with ATP, pH 7.5, 37°C Homo sapiens
0.27
-
tiazofurin Nrk1, with ATP, pH 7.5, 37°C Homo sapiens
1.3
-
uridine Nrk2, with ATP, pH 7.5, 37°C Homo sapiens
15
-
cytidine Nrk2, with ATP, pH 7.5, 37°C Homo sapiens
17
-
uridine Nrk1, with ATP, pH 7.5, 37°C Homo sapiens
30
-
cytidine Nrk1, with ATP, pH 7.5, 37°C Homo sapiens
30
-
beta-D-ribosylnicotinate Nrk2, with GTP, pH 7.5, 37°C Homo sapiens

Metals/Ions

Metals/Ions Comment Organism Structure
Mg2+ required Homo sapiens

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
ATP + beta-D-ribosylnicotinate Homo sapiens nicotinic acid riboside is a specific substrate of human Nrk enzymes ADP + nicotinate beta-D-ribonucleotide
-
?
additional information Homo sapiens Asp35 and Glu100 in Nrk2 are essential residues for function in vivo ?
-
?
additional information Homo sapiens Asp36 and Glu98 in Nrk1 are essential residues for function in vivo ?
-
?

Organism

Organism UniProt Comment Textmining
Homo sapiens Q9NPI5 Nrk2; Nrk2
-
Homo sapiens Q9NWW6 Nrk1; Nrk1
-

Purification (Commentary)

Purification (Comment) Organism
recombinant Nrk1 and Nrk2 from Escherichia coli by metal chelate affinity chromatography Homo sapiens
recombinant Nrk2 from Escherichia coli by metal chelate affinity chromatography Homo sapiens

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
ATP + beta-D-ribosylnicotinamide beta-D-ribosylnicotinamide is an NAD+ precursor utilized via the Nrk and Preiss-Hander pathways Homo sapiens ADP + nicotinamide beta-D-ribonucleotide
-
?
ATP + beta-D-ribosylnicotinate nicotinic acid riboside is a specific substrate of human Nrk enzymes Homo sapiens ADP + nicotinate beta-D-ribonucleotide
-
?
ATP + cytidine
-
Homo sapiens ADP + CMP
-
?
ATP + cytidine low activity with Nrk1 Homo sapiens ADP + CMP
-
?
ATP + nicotinamide mononucleotide
-
Homo sapiens ADP + nicotinamide mononucleotide phosphate
-
?
ATP + tiazofurin
-
Homo sapiens ADP + ?
-
?
ATP + tiazofurin a relatively good Nrk1 substrate Homo sapiens ADP + ?
-
?
ATP + uridine
-
Homo sapiens ADP + UMP
-
?
ATP + uridine low activity with Nrk1 Homo sapiens ADP + UMP
-
?
GTP + beta-D-ribosylnicotinate nicotinic acid riboside is a specific substrate of human Nrk enzymes Homo sapiens GDP + nicotinate beta-D-ribonucleotide
-
?
additional information Asp35 and Glu100 in Nrk2 are essential residues for function in vivo Homo sapiens ?
-
?
additional information Asp36 and Glu98 in Nrk1 are essential residues for function in vivo Homo sapiens ?
-
?
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 Homo sapiens ?
-
?
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 Homo sapiens ?
-
?

Subunits

Subunits Comment Organism
More the ADP-binding site includes P-loop sequence Gly-Val-Thr-Asn-Ser-Gly-Lys-Thr, residues 10-17 Homo sapiens

Synonyms

Synonyms Comment Organism
nicotinamide riboside kinase
-
Homo sapiens
NRK1
-
Homo sapiens
Nrk2
-
Homo sapiens

Temperature Optimum [°C]

Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
37
-
assay at Homo sapiens

Turnover Number [1/s]

Turnover Number Minimum [1/s] Turnover Number Maximum [1/s] Substrate Comment Organism Structure
0.21
-
uridine Nrk1, with ATP, pH 7.5, 37°C Homo sapiens
0.21
-
beta-D-ribosylnicotinamide Nrk1, with ATP, pH 7.5, 37°C Homo sapiens
0.34
-
beta-D-ribosylnicotinate Nrk1, with GTP, pH 7.5, 37°C Homo sapiens
0.34
-
beta-D-ribosylnicotinamide Nrk2, with ATP, pH 7.5, 37°C Homo sapiens
0.35
-
tiazofurin Nrk1, with ATP, pH 7.5, 37°C Homo sapiens
0.48
-
cytidine Nrk1, with ATP, pH 7.5, 37°C Homo sapiens
0.49
-
tiazofurin Nrk2, with ATP, pH 7.5, 37°C Homo sapiens
0.6
-
beta-D-ribosylnicotinate Nrk1, with ATP, pH 7.5, 37°C Homo sapiens
0.75
-
beta-D-ribosylnicotinate Nrk2, with ATP, pH 7.5, 37°C Homo sapiens
0.82
-
cytidine Nrk2, with ATP, pH 7.5, 37°C Homo sapiens
1.1
-
uridine Nrk2, with ATP, pH 7.5, 37°C Homo sapiens
1.7
-
beta-D-ribosylnicotinate Nrk2, with GTP, pH 7.5, 37°C Homo sapiens

pH Optimum

pH Optimum Minimum pH Optimum Maximum Comment Organism
7.5
-
assay at Homo sapiens

Cofactor

Cofactor Comment Organism Structure
ATP active with Nrk1 Homo sapiens
ATP specific for Nrk2 Homo sapiens
GTP active with Nrk1 Homo sapiens
additional information GTP is not with Nrk2 Homo sapiens

General Information

General Information Comment Organism
evolution the enzyme is structurally similar to Rossmann fold metabolite kinases Homo sapiens
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 Homo sapiens

kcat/KM [mM/s]

kcat/KM Value [1/mMs-1] kcat/KM Value Maximum [1/mMs-1] Substrate Comment Organism Structure
0.012
-
uridine Nrk1, with ATP, pH 7.5, 37°C Homo sapiens
0.016
-
cytidine Nrk1, with ATP, pH 7.5, 37°C Homo sapiens
0.055
-
cytidine Nrk2, with ATP, pH 7.5, 37°C Homo sapiens
0.057
-
beta-D-ribosylnicotinate Nrk2, with GTP, pH 7.5, 37°C Homo sapiens
0.85
-
uridine Nrk2, with ATP, pH 7.5, 37°C Homo sapiens
1.3
-
tiazofurin Nrk1, with ATP, pH 7.5, 37°C Homo sapiens
3.9
-
beta-D-ribosylnicotinate Nrk2, with ATP, pH 7.5, 37°C Homo sapiens
4.1
-
beta-D-ribosylnicotinamide Nrk1, with ATP, pH 7.5, 37°C Homo sapiens
4.5
-
tiazofurin Nrk2, with ATP, pH 7.5, 37°C Homo sapiens
5
-
beta-D-ribosylnicotinate Nrk1, with GTP, pH 7.5, 37°C Homo sapiens
5.4
-
beta-D-ribosylnicotinamide Nrk2, with ATP, pH 7.5, 37°C Homo sapiens
6.8
-
beta-D-ribosylnicotinate Nrk1, with ATP, pH 7.5, 37°C Homo sapiens