生命科学联合中心
Title：Translating the Precision Electrophile Signaling Code
Speaker： Yimon Aye, Ph.D.
Howard Milstein Assistant Professor
Time：2017-12-07（周四），13:00 -14:00 pm
Venue：北京大学化学与分子工程学院A717报告厅
Precisely timed and spatially regulated electrophilic chemical signals are the essence of biochemical redox signaling. However, defining the precise biological impacts of localized signals that engage with specific protein targets under physiologic conditions has proven to be highly challenging. This talk presents a unique set of proximity-directed chemical tools that enables interrogation into functional consequences of specific redox events through precision electrophile targeting in living systems. With this in vivo-validated redox-targeting toolset, we identify bona fide “first responders” that interact with native signaling electrophiles under electrophile-limited (true kcat/Km) conditions. Our data illuminate these first responders as novel signaling nodes, interchanging electrophile and conventional signaling codes such as phosphate and ubiquitin for decision making at organismal level. Our unique chemical biology toolset sets the stage for ruling in gain-of-function (or dominant loss-of-function) electrophilic modifications and relating them to phenotype in an unbiased experiment that is not hampered by functional redundancy. With the growing importance of covalent drugs in the treatment of various human disorders, our new ability to surgically examine precision covalent electrophile signaling mechanisms opens new avenues toward targeted therapeutics and novel target discovery.
