CHARACTERIZATION OF TWO NOVEL PATHWAYS IN MYCOBACTERIUM AS TARGETS AGAINST TUBER

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。 结核分枝杆菌是一种细菌病原体，导致结核病，世界？最致命的传染病，每年造成大约200万人死亡。 目前，全世界每三个人中就有一个人感染M。结核病是目前艾滋病患者死亡的主要原因。最近的数据表明，一个以前未被表征的血红素获取系统在M。结核病发病机制我建议的研究重点是获得这种新的分枝杆菌血红素收购系统的结构理解。 此外，我的建议包括一个新的途径，据推测参与脂肪酸代谢，已被证明是必不可少的生存鼠疫耶尔森氏菌在巨噬细胞，和M。结核病具有同源途径。 这些蛋白质的结构表征将使我们能够功能性地表征这一重要途径。在SSRL光束线上的时间对于了解这些途径中涉及的蛋白质的结构至关重要，其目标是基于结构的药物设计，用于开发抗结核病（TB）的治疗方法，包括多药耐药菌株和潜伏性TB感染。

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. Mycobacterium tuberculosis is a bacterial pathogen that causes tuberculosis, the worlds? most deadly infectious disease, which kills approximately two million people per year. Currently, one in three persons worldwide is infected with M. tuberculosis, and TB is also the current leading cause of death for AIDS patients. Recent data suggests that a previously uncharacterized heme acquisition system plays an important role in M. tuberculosis pathogenesis. My proposed research focuses on gaining a structural understanding of this novel mycobacterial heme acquisition system. Also, my proposal includes a novel pathway supposedly involved in fatty acid metabolism that has been shown to be essential for survival of Yersinia pestis in macrophages, and M. tuberculosis has a homologous pathway. Structural characterization of these proteins will allow us to functional characterize this important pathway. Time at the SSRL beam-line is paramount to the structural understanding of the proteins involved in these pathways with a goal of structure-based drug design for the development of therapeutics against tuberculosis (TB), which includes multi-drug resistant strains and latent TB infection.