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

多域酰基辅酶A羧化酶的晶体结构和基于结构的药物

• 批准号: 8170174
• 负责人: Shiou-Chuan Tsai
• 金额: $ 0.59万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-05-01 至 2011-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8170174
• 关键词: Acquired Immunodeficiency Syndrome; Acyl Coenzyme A; Biological; Cause of Death; Cell Wall; Cessation of life; Complex; Computer Retrieval of Information on Scientific Projects Database; Development; Drug Delivery Systems; Drug Design; Funding; Grant; Institution; Lead; Lipids; Medical; Mycobacterium tuberculosis; Patients; Pharmaceutical Preparations; Population; Preclinical Drug Evaluation; Research; Research Personnel; Resources; Role; Source; Structure; Time; Tuberculosis; United States National Institutes of Health; Virulence; base; lipid biosynthesis; pathogen; tuberculosis drugs

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.

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