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

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目和 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 结核病（TB）是目前艾滋病患者死亡的主要原因。其病原体结核分枝杆菌感染了世界三分之一的人口。细胞壁脂质对于结核分枝杆菌的生存、毒力和潜伏期发展至关重要。三种酰基辅酶 A 羧化酶 (ACCase)：AccD4、AccD5 和 AccD6 对于细胞壁脂质生物合成非常重要，其破坏会导致病原体死亡。 ACCase晶体结构的缺乏极大地阻碍了针对ACCase的新结核病药物的设计工作。 SSRL光束时间解析多亚基ACCase的晶体结构将具有科学意义，因为它将导致第一个多亚基ACCase复杂的晶体结构，并有助于定义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.