2QT0

Human nicotinamide riboside kinase 1 in complex with nicotinamide riboside and an ATP analogue

Summary for 2QT0

• Entry DOI: 10.2210/pdb2qt0/pdb
• Related: 2QSY 2QSZ 2QT1
• Descriptor: Nicotinamide riboside kinase 1, MAGNESIUM ION, PHOSPHOAMINOPHOSPHONIC ACID-ADENYLATE ESTER, ... (5 entities in total)
• Functional Keywords: non-protein kinase, nad+, nicotinamide riboside, nrk1, nicotinamide riboside kinase activity, nicotinic acid riboside kinase activity, nad biosynthesis, pyridine nucleotide biosynthesis, atp analogue, structural genomics, structural genomics consortium, sgc, alternative splicing, atp-binding, nucleotide-binding, transferase
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 1
• Total formula weight: 25159.12

Authors

Rabeh, W.M.,Tempel, W.,Nedyalkova, L.,Landry, R.,Arrowsmith, C.H.,Edwards, A.M.,Sundstrom, M.,Weigelt, J.,Bochkarev, A.,Brenner, C.,Park, H.,Structural Genomics Consortium (SGC) (deposition date: 2007-07-31, release date: 2007-08-14, Last modification date: 2024-11-06)

Primary citation

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-e263, 2007

PubMed Abstract: 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 nicotinamide adenine dinucleotide (NAD+) by phosphorylation and adenylylation. Crystal structures of human Nrk1 bound to nucleoside and nucleotide substrates and products revealed an enzyme structurally similar to Rossmann fold metabolite kinases and allowed the identification of active site residues, which were shown to be essential for human Nrk1 and Nrk2 activity in vivo. Although the structures account for the 500-fold discrimination between nicotinamide riboside and pyrimidine nucleosides, no enzyme feature was identified to recognize the distinctive carboxamide group of nicotinamide riboside. Indeed, nicotinic acid riboside is a specific substrate of human Nrk enzymes and is utilized in yeast in a novel biosynthetic pathway that depends on Nrk and NAD+ synthetase. Additionally, nicotinic acid riboside is utilized in vivo by Urh1, Pnp1, and Preiss-Handler salvage. Thus, crystal structures of Nrk1 led to the identification of new pathways to NAD+.

PubMed: 17914902
DOI: 10.1371/journal.pbio.0050263

Experimental method

X-RAY DIFFRACTION (1.92 Å)