结核分枝杆菌蛋白磷酸酶及其抑制剂研发进展advances in - 药学学报.pdfVIP

1420 药学学报 Acta Pharmaceutica Sinica 20 11, 46 ( 12) : 1420 1428 结核分枝杆菌蛋白磷酸酶及其抑制剂研发进展 1 2 1, 2* 滕铁山 , 王洪海 , 谢建平 ( 1. 西南大学生命科学学院现代生物医药研究所, 三峡库区生态环境与生物资源省部共建国家重点实验室, 重庆 400715; 2. 复旦大学生命科学学院遗传学研究所遗传工程国家重点实验室, 上海 200433) 摘要: 可逆的蛋白磷酸化调控多种生化反应。蛋白磷酸酶是结核分枝杆菌的关键分子, 不仅调控许多微生物 自身的代谢, 而且还可能干扰宿主细胞的信号传导。在结核分枝杆菌逃 宿主细胞的杀灭、阻止吞噬体与溶酶 体融合中蛋白磷酸酶也起着重要的作用。选择性抑制这些信号途径可能是抗结核药物研发的新思路。本文综述 了结核分枝杆菌蛋白磷酸酶MptpA、MptpB 、MstP 、SapM 及其底物、磷酸酶表达调控基因和网络、抑制剂研发 进展, 以期为新抗生素靶标提供信息。 关键词: 蛋白磷酸酶; 结核分枝杆菌; 药物靶标 中图分类号: R963 文献标识码:A 文章编号: 05 13-4870 (20 11) 12-1420-09 Advances in the study of Mycobacterium tuberculosis protein phosphatase and its inhibitors 1 2 1, 2* TENG Tie-shan , WANG Hong-hai , XIE Jian-ping (1. Institute of Modern Biop harmaceuticals, State Key Laboratory Breeding Base of Eco-Environment and Bio-Resource of the Three Gorges Area, School of Lif e Sciences, Southwest University, Chongqing 400715, China; 2. State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Science, Fudan University, Shanghai 200433, China) Abstract: Reversible protein phosphorylation regulates multiple biochemical events. Myc obacterium tuberculos is phosphatases play important roles in regulating the pathogen physiology and interference of host signaling. They are also involved in the evasion of host immune response and blockage of the phagosome- lysosome fusion. Selective inhibition of phosphatase represents an ideal new avenue of