肺炎链球菌胆碱合成代谢通路的结构和酶学研究

项目名称： 肺炎链球菌胆碱合成代谢通路的结构和酶学研究

项目编号： No.31470739

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 生物科学

项目作者： 陈宇星

作者单位： 中国科学技术大学

项目金额： 85万元

中文摘要： 肺炎链球菌是引起人类疾病的重要病原菌之一，可引起大叶性肺炎、脑膜炎、支气管炎等疾病，导致全球每年约160万人死亡。肺炎球链菌主要的致病因子是肺炎球菌溶血素及细胞壁荚膜。胆碱是肺炎链球菌细胞壁和夹膜上的重要组分，同时也是其生长所必须营养成分。胆碱对肺炎链球菌的分裂、转化、自溶以及表面毒性相关胆碱结合蛋白的形成具有至关重要的作用,因此胆碱合成代谢通路的研究将有助于我们更好地理解其致病机制。肺炎链球菌的胆碱合成代谢途径主要由lic基因簇编码的8个蛋白质催化的生化反应所组成。我们以这些lic蛋白为研究对象，用X射线晶体学的方法解析各个单一蛋白及其复合物的三维结构，同时结合微生物学、细胞生物学、生物化学的手段研究其生化和生理功能，以期阐明肺炎链球菌的胆碱代谢途径的结构和酶学基础，从而为研制新型的肺炎链球菌抑制剂和疫苗提供理论指导。

中文关键词： 肺炎链球菌；磷酸胆碱；蛋白质复合物；晶体结构；酶学

英文摘要： The major human pathogen Streptococcus pneumoniae is responsible for many infectious diseases, such as lobar pneumoniae, meningitis and bronchitis, which lead to approximately 1.6 million deaths annually in the world. The major virulencefactors include pneumococcal capsular polysaccharide, cell-wall fragments and hemolysin. Choline is an important chemical to constitute the pneumococcal cell wall and capsular. In addition, choline is also a nutrient required for thepneumococcal growth, normal transformability, the activity of autolysins, cell division and the anchoring a family of surface proteins which play important roles in pneumococcal infection. Therefore, the study of the pneumococcal choline catabolism pathway will help us to better understand the pathogenesis of S. pneumoniae.The pathway consists of eight proteins encoded by a gene cluster, termed lic. We aim to systematically solve the crystal structures of these proteins, and investigate their biological functions by using the methodologies of enzymology, microbiology and cell biology. The findings will elucidate the mechanism of pneumococcal choline catabolism pathway, andits contribution to the pathogenesis. Moreover, the structures will provide insights into the rational development of novel inhibitors and/or vaccines.

英文关键词： streptococcus pneumoniae;phosphocholine;protein complex;crystal structure;enzymology