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: 8362213
• 负责人: Shiou-Chuan Tsai
• 金额: $ 0.74万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-03-01 至 2012-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8362213
• 关键词: Acquired Immunodeficiency Syndrome; Acyl Coenzyme A; Biological; Cause of Death; Cell Wall; Cessation of life; Complex; Development; Drug Delivery Systems; Drug Design; Funding; Grant; Lead; Lipids; Medical; Mycobacterium tuberculosis; National Center for Research Resources; Patients; Pharmaceutical Preparations; Population; Preclinical Drug Evaluation; Principal Investigator; Radiation; Research; Research Infrastructure; Resources; Role; Source; Structure; Time; Tuberculosis; United States National Institutes of Health; Virulence; base; cost; lipid biosynthesis; pathogen; structural biology; tuberculosis drugs

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. 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.

该副本是利用资源的众多研究子项目之一 由NIH/NCRR资助的中心赠款提供。对该子弹的主要支持 而且，副投影的主要研究员可能是其他来源提供的 包括其他NIH来源。 列出的总费用可能 代表subproject使用的中心基础架构的估计量， NCRR赠款不直接向子弹或副本人员提供的直接资金。 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。