2G97

Crystal Structure of Visfatin/Pre-B Cell Colony Enhancing Factor 1/Nicotinamide Phosphoribosyltransferase In Complex with the Specific Inhibitor FK-866

2G97 の概要

• エントリーDOI: 10.2210/pdb2g97/pdb
• 関連するPDBエントリー: 2g95 2g96
• 分子名称: Nicotinamide phosphoribosyltransferase, (2E)-N-{4-[1-(benzenecarbonyl)piperidin-4-yl]butyl}-3-(pyridin-3-yl)prop-2-enamide (3 entities in total)
• 機能のキーワード: visfatin, pbef, namprtase, fk-866, rattus norvegicus, transferase
• 由来する生物種: Rattus norvegicus (Norway rat)
• 細胞内の位置: Nucleus : Q80Z29
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 111808.39

構造登録者

Kim, M.-K.,Eom, S.H. (登録日: 2006-03-05, 公開日: 2006-08-01, 最終更新日: 2023-10-25)

主引用文献

Kim, M.-K.,Lee, J.H.,Kim, H.,Park, S.J.,Kim, S.H.,Kang, G.B.,Lee, Y.S.,Kim, J.B.,Kim, K.K.,Suh, S.W.,Eom, S.H.
Crystal Structure of Visfatin/Pre-B Cell Colony-enhancing Factor 1/Nicotinamide Phosphoribosyltransferase, Free and in Complex with the Anti-cancer Agent FK-866
J.Mol.Biol., 362:66-77, 2006

PubMed Abstract: Visfatin/pre-B cell colony-enhancing factor 1 (PBEF)/nicotinamide phosphoribosyltransferase (NAmPRTase) is a multifunctional protein having phosphoribosyltransferase, cytokine and adipokine activities. Originally isolated as a cytokine promoting the differentiation of B cell precursors, it was recently suggested to act as an insulin analog via the insulin receptor. Here, we describe the first crystal structure of visfatin in three different forms: apo and in complex with either nicotinamide mononucleotide (NMN) or the NAmPRTase inhibitor FK-866 which was developed as an anti-cancer agent, interferes with NAD biosynthesis, showing a particularly high specificity for NAmPRTase. The crystal structures of the complexes with either NMN or FK-866 show that the enzymatic active site of visfatin is optimized for nicotinamide binding and that the nicotinamide-binding site is important for inhibition by FK-866. Interestingly, visfatin mimics insulin signaling by binding to the insulin receptor with an affinity similar to that of insulin and does not share the binding site with insulin on the insulin receptor. To predict binding sites, the potential interaction patches of visfatin and the L1-CR-L2 domain of insulin receptor were generated and analyzed. Although the relationship between the insulin-mimetic property and the enzymatic function of visfatin has not been clearly established, our structures raise the intriguing possibility that the glucose metabolism and the NAD biosynthesis are linked by visfatin.

PubMed: 16901503
DOI: 10.1016/j.jmb.2006.06.082

実験手法

X-RAY DIFFRACTION (2.9 Å)