2QT0

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

2QT0 の概要

• エントリーDOI: 10.2210/pdb2qt0/pdb
• 関連するPDBエントリー: 2QSY 2QSZ 2QT1
• 分子名称: Nicotinamide riboside kinase 1, MAGNESIUM ION, PHOSPHOAMINOPHOSPHONIC ACID-ADENYLATE ESTER, ... (5 entities in total)
• 機能のキーワード: 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
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 25159.12

構造登録者

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) (登録日: 2007-07-31, 公開日: 2007-08-14, 最終更新日: 2024-11-06)

主引用文献

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

実験手法

X-RAY DIFFRACTION (1.92 Å)