基于机制的MenE抑制剂，MenE是一种参与细菌甲萘醌生物合成的酰基辅酶A合成酶。
Mechanism-based inhibitors of MenE, an acyl-CoA synthetase involved in bacterial menaquinone biosynthesis.
作者信息
Lu Xuequan, Zhang Huaning, Tonge Peter J, Tan Derek S
机构信息
Molecular Pharmacology & Chemistry Program and Tri-Institutional Research Program, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, Box 422, New York, NY 10065, USA.
出版信息
Bioorg Med Chem Lett. 2008 Nov 15;18(22):5963-6. doi: 10.1016/j.bmcl.2008.07.130. Epub 2008 Aug 12.
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.
摘要
甲萘醌（维生素K(2)）是包括结核分枝杆菌和金黄色葡萄球菌在内的许多病原体中电子传递链的重要组成部分，甲萘醌生物合成是抗生素药物研发的一个潜在靶点。我们在此报告了一系列基于机制的MenE抑制剂，MenE是一种酰基辅酶A合成酶，在甲萘醌生物合成过程中催化邻琥珀酰苯甲酸（OSB）的腺苷化和硫酯化反应。最有效的化合物对MenE的抑制作用IC(50)值为5.7微摩尔。
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