Title of article :
Crystal Structure of Visfatin/Pre-B Cell Colony-enhancing Factor 1/Nicotinamide Phosphoribosyltransferase, Free and in Complex with the Anti-cancer Agent FK-866
Author/Authors :
Mun-Kyoung Kim، نويسنده , , Jun Hyuck Lee، نويسنده , , Hun Kim، نويسنده , , Soo Jeong Park، نويسنده , , Sung Hyun Kim، نويسنده , , Gil Bu Kang، نويسنده , , Yun Sok Lee، نويسنده , , Jae Bum Kim، نويسنده , , Kyeong Kyu Kim، نويسنده , , Se Won Suh، نويسنده , , Soo Hyun Eom، نويسنده ,
Issue Information :
روزنامه با شماره پیاپی سال 2006
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.
Keywords :
Visfatin , pre-B cell colony-enhancing factor 1 , X-ray structure , nicotinamide phosphoribosyltransferase , insulin receptor
Journal title :
Journal of Molecular Biology
Journal title :
Journal of Molecular Biology