3G8E

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

Summary for 3G8E

• Entry DOI: 10.2210/pdb3g8e/pdb
• Related: 2G96 2G97
• Descriptor: 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)
• Functional Keywords: protein-ligand complex, is001, cytoplasm, glycosyltransferase, nucleus, phosphoprotein, pyridine nucleotide biosynthesis, transferase
• Biological source: Rattus norvegicus (rat)
• Cellular location: Cytoplasm: Q80Z29
• Total number of polymer chains: 2
• Total formula weight: 112074.63

Authors

Kang, G.B.,Bae, M.H.,Kim, M.K.,Im, I.,Kim, Y.C.,Eom, S.H. (deposition date: 2009-02-12, release date: 2009-08-18, Last modification date: 2023-11-01)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (3 Å)