报告时间：2019年4月13日上午9:00

报告地点：杭师大仓前校区行政楼417会议室

学术报告题目1：Development of new antibiotics to treat tuberculosis（设计抗结核的新型抗生素）

报告人1：杨海涛教授

杨海涛教授简介：

杨海涛教授长期从事对人类健康造成重大威胁的病原体的研究（如结核杆菌、寨卡病毒、“非典”病毒和艾滋病病毒等）及抗感染药物的研发，通过解析这些病毒的关键药物靶点的原子分辨率结构，了解宿主与病毒之间的精确相互作用，开发抗病毒新药和新疗法。杨海涛教授在《Cell》、《PNAS》、《PLoS Biology》、《Nature Struct. Mol. Biol》等学术期刊上发表了多篇学术论文。

杨海涛教授现任或曾任的职务包括上海科技大学免疫化学研究所研究员、天津国际生物医药联合研究院抗感染药物研发中心主任、天津大学生命科学学院副院长、国家重点研发计划重点专项总体专家组成员、“973”计划青年项目首席科学家、波兰国家科学基金外审专家、国家“重大新药创制”科技重大专项评审专家和长江学者奖励计划评审专家，曾入选国家“青年千人计划”，获得了中国产学研合作促进奖、中国侨界贡献奖、科学中国人年度人物等荣誉。

报告摘要：

Despite intensive efforts to discover highly effective treatments to eradicate tuberculosis (TB), it remains as a major threat to global human health. For this reason, new TB drugs directed towards new targets are highly coveted.

MmpLs (Mycobacterial membrane proteins Large) which play crucial roles in transporting lipids, polymers and immunomodulators, and that also extrude therapeutic drugs, are amongst the most important therapeutic drug targets to emerge in recent times. Here, crystal structures of Mycobacterial MmpL3 alone and in complex with four TB drug candidates including SQ109 (in Phase 2b-3 clinical trials) are reported. MmpL3 consists of a periplasmic pore domain and a twelve-helix transmembrane domain. Two Asp-Tyr pairs centrally located in this domain appear to be key facilitators of proton-translocation. SQ109, AU1235 and ICA38 bind inside the transmembrane region and disrupt these Asp-Tyr pairs. Strikingly, rimonabant, the first CB1 antagonist, was also found to target the same binding pocket. It is remarkable that rimonabant adopts completely different binding modes to inhibit mycobacterial MmpL3 and human CB1 receptor. Since MmpL3 and its orthologues are well conserved across mycobacteria and corynebacteria, these results may facilitate the development of new drugs which are broadly effective against these and other human pathogenic infectious diseases including TB, leprosy and diphtheria. In addition, this is the first report describing structures of drug candidates which can block the proton motive force to inhibit an RND family member, many of which are important targets for anti-bacterial drug discovery. These data will therefore provide inspiration for the design of new classes of antibiotics.

学术报告题目2：中药活性成分合成生物学研究

报告人2：高伟教授

高伟教授简介：

高伟教授为首都医科大学教授、博导，药学院副院长（主持工作），首都医科大学校学术委员会委员，美国CSHL访问学者。全国百篇优秀博士学位论文、国家自然科学优秀青年基金和科技部“863 计划”青年科学家项目获得者；入选“万人计划”科技创新领军人才、“万人计划”青年拔尖人才、教育部青年长江学者、科技部中青年科技创新领军人才和北京市“高创计划”领军人才等。主要从事中药资源与分子生药学研究，在中药活性成分及天然药物基因功能鉴定、生源途径解析及合成生物学研究领域取得了创新性成果，在JACS 、New Phytologist、Plant Journal、Organic Letters等国家知名期刊发表系列论文。获省部级奖6项，授权发明专利5项。兼任中华中医药学会青年委员会主任委员、中国中西医结合学会分子生药学分会秘书长、中国植物学会药用植物及植物药专业委员会副秘书长等。