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

该子项目是利用 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来源获得主要资金， 因此可以在其他CRISP条目中表示。列出的机构是 中心，不一定是研究者的机构。 结核病是目前艾滋病患者的主要死因。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M.结核三种酰基辅酶A羧化酶（ACCases），AccD 4、AccD 5和AccD 6，在细胞壁脂质生物合成中是重要的，其破坏导致病原体死亡。ACCase晶体结构的缺乏极大地阻碍了靶向ACCase的新型结核病药物的药物设计工作。SSRL束时间解决多亚基ACCase的晶体结构将具有科学意义，因为它将导致有史以来第一个多亚基ACCase复杂晶体结构，并有助于定义AccD 4 -6的生物学作用。它的医学意义在于基于ACCase晶体结构的结构药物筛选。

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.