3G8E

Crystal Structure of Rattus norvegicus Visfatin/PBEF/Nampt in Complex with an FK866-based inhibitor

3G8E の概要

• エントリーDOI: 10.2210/pdb3g8e/pdb
• 関連するPDBエントリー: 2G96 2G97
• 分子名称: Nicotinamide phosphoribosyltransferase, 3-[(1E)-3-oxo-3-({4-[1-(phenylcarbonyl)piperidin-4-yl]butyl}amino)prop-1-en-1-yl]-1-beta-D-ribofuranosylpyridinium (2 entities in total)
• 機能のキーワード: protein-ligand complex, is001, cytoplasm, glycosyltransferase, nucleus, phosphoprotein, pyridine nucleotide biosynthesis, transferase
• 由来する生物種: Rattus norvegicus (rat)
• 細胞内の位置: Cytoplasm: Q80Z29
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 112074.63

構造登録者

Kang, G.B.,Bae, M.H.,Kim, M.K.,Im, I.,Kim, Y.C.,Eom, S.H. (登録日: 2009-02-12, 公開日: 2009-08-18, 最終更新日: 2023-11-01)

主引用文献

Kang, G.B.,Bae, M.H.,Kim, M.K.,Im, I.,Kim, Y.C.,Eom, S.H.
Crystal structure of Rattus norvegicus Visfatin/PBEF/Nampt in complex with an FK866-based inhibitor
Mol.Cells, 27:667-671, 2009

PubMed Abstract: Visfatin (Nampt/PBEF) plays a pivotal role in the salvage pathway for NAD(+) biosynthesis. Its potent inhibitor, FK866, causes cellular NAD(+) levels to decline, thereby inducing apoptosis in tumor cells. In an effort to improve the solubility and binding interactions of FK866, we designed and synthesized IS001, in which a ribose group is attached to the FK866 pyridyl ring. Here, we report the crystal structure of rat visfatin in complex with IS001. Like FK866, IS001 is positioned at the dimer interface, and all of the residues that interact with IS001 are involved in hydrophobic or pi-pi-stacking interactions. However, we were unable to detect any strong interactions between the added ribose ring of IS001 and visfatin, which implies that a bulkier modifying group is necessary for a tight interaction. This study provides additional structure-based information needed to optimize the design of visfatin inhibitors.

PubMed: 19533035
DOI: 10.1007/s10059-009-0088-x

実験手法

X-RAY DIFFRACTION (3 Å)