1,4-DIHYDROXY-2-NAPHTHOYL-COA SYNTHASE IN COMPLEX WITH HIGH AFFINITY SUBSTRATE A

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 MenB处于将分支酸盐转化为甲基萘醌的生物合成途径的中心，甲基萘醌是结核分枝杆菌厌氧呼吸过程中脂质中电子穿梭所需的。靶向MenB并因此靶向甲基萘醌生物合成的抑制剂可潜在地用于治疗潜伏性TB，因为预期呼吸即使在休眠状态下也是必需的。大多数开发中的药物都是针对结核病的活动形式，但潜伏形式仍然是一个很大的问题。我们已经开发出对MenB具有中等亲和力的抑制剂，并且这里获得的结构将用于具有改进活性的抑制剂的合理设计。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. MenB is in the center of the biosynthetic pathway converting chorismate into menaquinone, which is required for electron shuttling in lipids in the anaerobic respiration process of Mycobacterium tuberculosis. Inhibitors targeting MenB and therefore menaquinone biosynthesis can potentially be used for treating latent TB since respiration is expected to be necessary even in the dormant state. Most developing drugs are targeting the active form of TB but the latent form remains a great concern. We have developed inhibitors with moderate affinity for MenB and structures obtained here will be used for rational design of inhibitors with improved activities.