Structural highlights
Function
NAMPT_RAT Catalyzes the condensation of nicotinamide with 5-phosphoribosyl-1-pyrophosphate to yield nicotinamide mononucleotide, an intermediate in the biosynthesis of NAD. It is the rate limiting component in the mammalian NAD biosynthesis pathway (By similarity).
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
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.
Crystal structure of Rattus norvegicus Visfatin/PBEF/Nampt in complex with an FK866-based inhibitor.,Kang GB, Bae MH, Kim MK, Im I, Kim YC, Eom SH Mol Cells. 2009 Jun;27(6):667-71. Epub 2009 Jun 12. PMID:19533035[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Kang GB, Bae MH, Kim MK, Im I, Kim YC, Eom SH. Crystal structure of Rattus norvegicus Visfatin/PBEF/Nampt in complex with an FK866-based inhibitor. Mol Cells. 2009 Jun;27(6):667-71. Epub 2009 Jun 12. PMID:19533035 doi:10.1007/s10059-009-0088-x
