抗结核杆菌新药发现靶点蛋白的研究进展  

Current Progress for Anti-M7B Targets Discovery

作　　者：娄智勇[1,2] 

机构地区：[1]清华大学结构生物学实验室 [2]清华大学医学院,北京100084

出　　处：《生物物理学报》2011年第10期828-838,共11页Acta Biophysica Sinica

基　　金：国家自然科学基金(30870486);国家重大专项(2009ZX09311-001;2009ZX10004-304)~~

摘　　要：结核病是世界范围内导致人类死亡的重大传染性疾病,而结核杆菌(Mycobacterium tuberculosis)则是导致结核病的病原体。早期的药物研发已经开发出对结核杆菌具有良好抑制效果的药物,并在临床应用中产生了很好的效果。然而近年来,随着药物的使用等综合因素的作用,耐药性(multi-drug-resistant,MDR)结核杆菌和超级耐药性(extensively-drug-resistant,XDR)结核杆菌感染病例不断出现,使得目前抗结核病药物的药效急剧降低,同时伴随着结核杆菌与HIV-1等病原体的共感染等问题,亟需开发针对全新靶点的抗结核药物,以应对日趋严重的结核病发生趋势。结核杆菌基因组测序的完成,使人们对结核杆菌编码的4000余个基因有了较为充分的认识,能够确定对于结核杆菌的生命周期起关键作用的靶点蛋白,并针对这些关键靶点蛋白进行药物开发。鉴于结核杆菌新药研发中所关注的重要靶点蛋白在结核杆菌生命周期中的功能不尽相同,本文将对这些靶点蛋白结构和功能研究的进展进行综述和总结。Tuberculosis（TB） is one of the most severe worldwide,infectious diseases and Mycobacterium tuberculosis was identified to be the causative agent for most TB.Although in the last decades several anti-TB drug with high efficacy were discovered,the emergence of multi-drug-resistant and extensively-drug-resistant TB in recent years and co-infection of TB with HIV-1 cause extensive morbidity and death and thus it＇s required to characterize new drugs with novel targets and mechanism for anti-drug resistant TB therapy.Currently,anti-TB drug discoveries for new targets mostly focus on the essential proteins in the pathway of biomolecules synthesis,cell wall synthesis,DNA metabolism,etc.The structural and biochemical information of these target proteins can help us to understand the structure and mechanism,this set up biochemical assays for drug discovery.In this review,we will discuss the recent progress on novel targets for structure-based anti-M.tuberculosis drug discovery.

关 键 词：MYCOBACTERIUM TUBERCULOSIS 结核杆菌 新药发现 靶点蛋白 结构与功能 

分 类 号：Q71[生物学—分子生物学]