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; 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.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 结核病（TB）是艾滋病患者目前的主要死亡原因。它的病原体，结核分枝杆菌，感染了世界人口的三分之一。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。三个酰基-COA羧化酶（ACCD4，ACCD5和ACCD6）对于细胞壁脂质生物合成很重要，它们的破坏会导致病原体死亡。缺乏ACCASE晶体结构极大地阻碍了针对Accase的新结核药物的药物设计工作。求解多生Accase的晶体结构的SSRL光束时间在科学上是显着意义的，因为它将导致有史以来第一个多支化合物ACCASE复杂晶体结构，并有助于定义ACCD4-6的生物学作用。它的医学意义在于基于ACCASE晶体结构的基于结构的药物筛查。