title: Mechanism-based inhibitors of MenE, an acyl-CoA synthetase involved in bacterial menaquinone biosynthesis.
abstract: 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.
authors.affiliation: Molecular Pharmacology & Chemistry Program and Tri-Institutional Research Program, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, Box 422, New York, NY 10065, USA.
authors.forename: Xuequan
authors.initials: X
authors.lastname: Lu
authors.forename: Huaning
authors.initials: H
authors.lastname: Zhang
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Tonge
authors.forename: Derek S
authors.initials: DS
authors.lastname: Tan