项目名称: 结核杆菌关键蛋白结构与功能研究
项目编号: No.30870486
项目类型: 面上项目
立项/批准年度: 2009
项目学科: 生物科学
项目作者: 娄智勇
作者单位: 清华大学
项目金额: 32万元
中文摘要: 结核杆菌(Mycobecterium Tuberculosis)是引起结核病的病原体。做为全球致死最多的传染性疾病,20 世纪90 年代以来,随着耐药结核分枝杆菌出现,特别是耐多药结核病的急剧增多,全球结核病疫情日益严重。中国做为全球22 个高负担防治结核的国家和地区之一,耐药结核病疫情是全球最重的国家之一,造成众多的感染和死亡病例。国际结核结构基因组学协会已经牵头进行此类研究,截至到2008 年1 月,该组织已经解出结核杆菌蛋白结构205 个,根据其中一些关键蛋白的结构,国外制药公司已开发出一些较有前途的药物或者药物前体。本研究立足于包括ICL、FabD、FabD2、TB iciA、GlmU 等已发现的结核杆菌生命周期中特异性的关键蛋白,通过解析蛋白以及与抑制剂/底物的复合物的晶体结构,了解和阐明这些关键蛋白在结核杆菌中发挥的具体功能和作用机制,更为基于结构的抗结核创新药物的研发奠定良好的基础。
中文关键词: 结核杆菌;关键靶点蛋白;晶体结构;作用机理;新药筛选与设计
英文摘要: The increasing incidence of Mycobacterium tuberculosis (TB) is a significant health problem that has profoundly impacted the treatment of infectious diseases. In 2006, about 9.2 million new cases of TB occurred, and around 0.7 million (7.7%) was HIVpositive by the World Health Organization. TB is responsible for tens of thousands of deaths world wide per year. Until 2008, TB Structural Genomics Consortium has determined 205 crystal structures of key proteins in TB life cycle. Based on these structures, pharmacy companies developed several potential anti-TB drugs or lead compounds. This study will focus on the key proteins in TB life cycle, including ICL, FabD, FabD2, TB icicA and Glmu, try to find some potential inhibitors and determine the crystal structures of these proteins and protein/inhibitor complexes. Moreover, these structures will be helpful to understand the clear functions of these proteins.
英文关键词: Mycobacterium tuberculosis; key proteins; crystal structure; mechanism; drug screen and design