Mechanism-based inhibitors of MenE, an acyl-CoA synthetase involved in bacterial menaquinone biosynthesis.
Menaquinone (vitamin K(2)) is an essential component of the electron transfer chain in many pathogens, including Mycobacterium tuberculosis and Staphylococcus aureus, and menaquinone biosynthesis is a potential target for antibiotic drug discovery. We report herein a series of mechanism-based inhibitors of MenE, an acyl-CoA synthetase that catalyzes adenylation and thioesterification of o-succinylbenzoic acid (OSB) during menaquinone biosynthesis. The most potent compound inhibits MenE with an IC(50) value of 5.7microM.
Lu
Xuequan
X
Molecular Pharmacology & Chemistry Program and Tri-Institutional Research Program, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, Box 422, New York, NY 10065, USA.
Zhang
Huaning
H
Tonge
Peter J
PJ
Tan
Derek S
DS