ChBE Seminar Series: Myles Poulin, UMD
Using Isotope Effects as a Tool to Design Enzyme Inhibitors
Transition state analogs are amongst the most potent enzyme inhibitors. The design of transition state analogs is aided by detailed information about enzyme transition state structure that can be obtained through a combination of experimental kinetic isotope effect measurements and quantum chemical calculations. Here I will present how we have used kinetic isotope effect measurements to study the transition state structure of protein lysine methyltransferase enzymes. The methylation of histone proteins, by protein lysine methyltransferase enzymes play an essential role in chromatin remodeling and the regulation of gene transcription. Misregulation of these histone marks can lead to aberrant transcription and has been associated with the development of cancer. The transition state structure determined from KIE data will guide the design of transition state analog inhibitors of PKMT enzymes that have potential as cancer chemotherapeutics.
Myles Poulin grew up in the small town of Smithers, British Columbia. He attended the University of Northern British Columbia (UNBC) and graduated with a B.Sc. in Biochemistry & Molecular Biology in 2007. Afterwards, he completed a Ph.D. in Chemistry from the University of Alberta in 2012 under the guidance of Prof. Todd L. Lowary where his dissertation research focused on the synthesis and evaluation of substrate analogs to study enzymes involved in furanose sugar biosynthesis. He then joined the laboratory of Vern L. Schramm at Albert Einstein College of Medicine in New York as a postdoctoral fellow. There he worked in collaboration with researchers from GlaxoSmithKline to investigate the transition state structure of protein lysine methyltransferase enzymes. In the fall of 2016, he joined the Department of Chemistry and Biochemistry at the University of Maryland College Park as an Assistant Professor.