CRYSTAL STRUCTURES OF MULTI-DOMAIN ACYL-COA CARBOXYLASE AND STRUCTURE-BASED DRUG

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 结核病(TB)是目前艾滋病患者的主要死亡原因。它的病原体是结核分枝杆菌，感染着世界三分之一的人口。细胞壁脂类对结核分枝杆菌的生存、毒力和潜伏期发展是必不可少的。AccD4、AccD5和AccD6三个酰基辅酶A羧化酶(AccDase)在细胞壁脂生物合成中起重要作用，它们的干扰会导致病原菌死亡。ACCase晶体结构的缺乏极大地阻碍了针对ACCase的新药的药物设计工作。SSRL束时间解算多亚基ACCase的晶体结构将具有重要的科学意义，因为它将导致首次发现多亚基ACCase的复杂晶体结构，并有助于确定AccD4-6的生物学作用。其医学意义在于基于ACCase晶体结构的药物筛选。

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. Tuberculosis (TB) is the current leading cause of death for AIDS patients. Its pathogen, Mycobacterium tuberculosis, infects one-third of the world population. Cell wall lipids are essential for the survival, virulence and latency development of M. tuberculosis. Three acyl-CoA carboxylases (ACCases), AccD4, AccD5 and AccD6, are important for cell wall lipid biosynthesis, whose disruption leads to pathogen death. The lack of ACCase crystal structures has greatly hampered the drug design effort of new tuberculosis drugs that target at ACCase. SSRL beam time to solve crystal structures of multi-subunit ACCase will be scientifically significant, because it will lead to the first ever multi-subunit ACCase complex crystal structure, and help define the biological roles of AccD4-6. Its medical significance lies in structure-based drug screening based on ACCase crystal structures.