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

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 在结核分枝杆菌厌氧呼吸过程中，膜蛋白B处于将分支酸转化为甲喹酮的生物合成途径的中心，这是在脂质中进行电子穿梭所必需的。以MenB为靶点的抑制剂因此可以潜在地用于治疗潜伏性结核病，因为即使在休眠状态下呼吸也是必要的。大多数开发中的药物针对的是活跃形式的结核病，但潜伏形式仍然是一个非常令人担忧的问题。我们已经开发出与MenB具有中等亲和力的抑制剂，所获得的结构将用于合理设计具有更高活性的抑制剂。

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.