2G95

Crystal Structure of Visfatin/Pre-B Cell Colony Enhancing Factor 1/Nicotinamide Phosphoribosyltransferase

Summary for 2G95

• Entry DOI: 10.2210/pdb2g95/pdb
• Related: 2g96 2g97
• Descriptor: Nicotinamide phosphoribosyltransferase (2 entities in total)
• Functional Keywords: visfatin, pbef, namprtase, rattus norvegicus, transferase
• Biological source: Rattus norvegicus (Norway rat)
• Cellular location: Cytoplasm: Q80Z29
• Total number of polymer chains: 2
• Total formula weight: 111025.38

Authors

Kim, M.-K.,Eom, S.H. (deposition date: 2006-03-05, release date: 2006-08-01, Last modification date: 2024-04-03)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (1.9 Å)