3DGR

Crystal structure of human NAMPT complexed with ADP analogue

3DGR の概要

• エントリーDOI: 10.2210/pdb3dgr/pdb
• 関連するPDBエントリー: 3DHD 3DHF 3DKJ 3DKL
• 分子名称: Nicotinamide phosphoribosyltransferase, PHOSPHOMETHYLPHOSPHONIC ACID ADENOSYL ESTER (3 entities in total)
• 機能のキーワード: transferase, nmprtase, visfatin, adenosine 5'-(alpha, beta-methylene)diphosphate, alternative splicing, cytoplasm, glycosyltransferase, phosphoprotein, polymorphism, pyridine nucleotide biosynthesis
• 由来する生物種: Homo sapiens
• 細胞内の位置: Nucleus : P43490
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 110460.67

構造登録者

Ho, M.,Burgos, E.S.,Almo, S.C.,Schramm, V.L. (登録日: 2008-06-15, 公開日: 2009-08-18, 最終更新日: 2023-08-30)

主引用文献

Burgos, E.S.,Ho, M.C.,Almo, S.C.,Schramm, V.L.
A phosphoenzyme mimic, overlapping catalytic sites and reaction coordinate motion for human NAMPT.
Proc.Natl.Acad.Sci.USA, 106:13748-13753, 2009

PubMed Abstract: Nicotinamide phosphoribosyltransferase (NAMPT) is highly evolved to capture nicotinamide (NAM) and replenish the nicotinamide adenine dinucleotide (NAD(+)) pool during ADP-ribosylation and transferase reactions. ATP-phosphorylation of an active-site histidine causes catalytic activation, increasing NAM affinity by 160,000. Crystal structures of NAMPT with catalytic site ligands identify the phosphorylation site, establish its role in catalysis, demonstrate unique overlapping ATP and phosphoribosyltransferase sites, and establish reaction coordinate motion. NAMPT structures with beryllium fluoride indicate a covalent H247-BeF(3)(-) as the phosphohistidine mimic. Activation of NAMPT by H247-phosphorylation causes stabilization of the enzyme-phosphoribosylpyrophosphate complex, permitting efficient capture of NAM. Reactant and product structures establish reaction coordinate motion for NAMPT to be migration of the ribosyl anomeric carbon from the pyrophosphate leaving group to the nicotinamide-N1 while the 5-phosphoryl group, the pyrophosphate moiety, and the nicotinamide ring remain fixed in the catalytic site.

PubMed: 19666527
DOI: 10.1073/pnas.0903898106

実験手法

X-RAY DIFFRACTION (2.1 Å)