Mol. Cells 2009; 27(6): 667-671
Published online June 12, 2009
https://doi.org/10.1007/s10059-009-0088-x
© The Korean Society for Molecular and Cellular Biology
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 ?-?-stacking interactions. However, we were unable to detect any strong interac-tions 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.
Keywords crystal structure, FK866, nicotinamide phosphoribosyltransferase (Nampt), pre-B-cell colony-enhancing factor (PBEF), visfatin
Mol. Cells 2009; 27(6): 667-671
Published online June 30, 2009 https://doi.org/10.1007/s10059-009-0088-x
Copyright © The Korean Society for Molecular and Cellular Biology.
Gil Bu Kang, Man-Ho Bae, Mun-Kyoung Kim, Isak Im, Yong-Chul Kim, and Soo Hyun Eom
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 ?-?-stacking interactions. However, we were unable to detect any strong interac-tions 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.
Keywords: crystal structure, FK866, nicotinamide phosphoribosyltransferase (Nampt), pre-B-cell colony-enhancing factor (PBEF), visfatin
Jinsook Ahn, Inseong Jo, Soyeon Jeong, Jinwook Lee, and Nam-Chul Ha
Mol. Cells 2023; 46(5): 309-318 https://doi.org/10.14348/molcells.2023.2144Sang-Sang Park, Sangho Lee, and Dong-Kwon Rhee
Mol. Cells 2021; 44(3): 179-185 https://doi.org/10.14348/molcells.2021.2235Hye Seon Lee, Yeajin Mo, Ho-Chul Shin, Seung Jun Kim, and Bonsu Ku
Mol. Cells 2020; 43(12): 1035-1045 https://doi.org/10.14348/molcells.2020.0192