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

1,4-二羟基-2-萘酰基-COA 合酶与高亲和力底物 A 复合

• 批准号: 8170660
• 负责人: MIGUEL GARCIA-DIAZ
• 金额: $ 0.54万
• 依托单位: BROOKHAVEN SCIENCE ASSOC-BROOKHAVEN LAB
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-07-01 至 2011-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8170660
• 关键词: Affinity; Anabolism; Complex; Computer Retrieval of Information on Scientific Projects Database; Crystallography; Drug Delivery Systems; Electrons; Funding; Grant; Institution; Lipids; Mycobacterium tuberculosis; Pathway interactions; Process; Research; Research Personnel; Resources; Respiration; Source; Structure; United States National Institutes of Health; Vitamin K 2; design; improved; inhibitor/antagonist

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. 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.

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 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。针对MenB以及甲基喹啉酮生物合成的抑制剂可能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。