结核病是世界上仅次于艾滋病的第二大传染病。目前主要存在三大问题：一. 疫苗年代太久； 二. 主要药物使用历史过长，耐药性日趋严重； 三. 诊断缺乏标识物，检出率低。其中多抗药性和广泛抗药性是最主要的问题，已严重威胁临床治疗。因此，现在关键任务是开发新的疫苗和抗生素。我们利用结构生物学、生物化学、遗传学及细胞生物学等方法，研究结核杆菌致病相关重要蛋白，尤其重点研究潜在药物靶标膜蛋白。我们针对结核杆菌呼吸链上必需的电子载体Ubiquinone 和Menaquinone的关键合成酶MenA和UbiA进行结构和功能研究，揭示该类膜蛋白酶的催化机制。同时我们对来源人的MenA同源物蛋白UBIAD1进行结构和功能研究。通过MenA 和UBIAD1的结构比较，拟在MenA蛋白晶体结构基础上进行抑制剂筛选、药物设计和开发，力争筛选到高选择性抑制剂，为进一步的研究提供理论依据和指导，为医药转化奠定基础。

Tuberculosis (TB) is still remained a major global health problem. It is the second infectious disease leading to death among infectious diseases worldwide after the human immunodeficiency virus (HIV). Now there are three big problems unresolved, such as the etiological agent and diagnostic tests of tuberculosis, hampers development of much-needed drugs and vaccines. Drug resistance is the most heavily thing among these, including MDR (multidrug resistance) and XDR (extensively drug resistance). In order to address above problems, new vaccine and new drugs are urgently needed. Here, our aims are to develop drugs for cure tuberculosis mainly via means of structure biology, combination methods of biochemistry, genetics and cell biology. We are investigating, the potential drug target of mycobacterium tuberculosis (mTB), MenA and UbiA, which are responsible for biosynthesis of ubiquinone and menaquinone in cell membranes, respectively. Ubiquinone and menaquinone, fat-soluble molecules, take as electron carrier in electron transfer chain in bacteria. We are aiming to determine structures of UbiA and MenA for rationale design inhibitors and furthering to know the inhibition-mechanisms. We also investigate structure and functions of MenA homologue UBIAD1 originated from humans, and will screen the higher selective inhibitors based on aligned structures between MenA and UBIAD1. Our studies will provide the solid foundation for drugs design and the theory basis for its further clinical transformation.