Chemistry Seminar Series: J. Scott Prosser

Friday, October 11, 2019 1:00 pm - 1:00 pm EDT (GMT -04:00)

Molecular and Mechanistic Underpinnings of Signal Transduction in Membranes - NMR Inspired Studies of the Conformational Landscape in Enzymes & GPCRs

R. Scott Prosser
Departments of Chemistry & Biochemistry,
University of Toronto, Canada

Friday, October 11, 2019
1:00 p.m.
C2-361 (Reading Room)


Illustration of the role of this ensemble along the reaction coordinate pathway
In the last decade, X-ray crystallography and cryo-electron microscopy have brought about a renaissance in structural biology. Recent atomic-resolution structures of both soluble and membrane associated proteins provide the possibility of mechanistic explanations of function and have renewed efforts in drug discovery. However, the “structure-function” perspective ignores the reality of protein dynamics and the fact that most proteins adopt a fluid ensemble of functional conformers (states). We are interested in the role of this ensemble along the reaction coordinate pathway. This talk will review studies associated with a homodimeric enzyme, fluroacetate dehalogenase, and the role of the ensemble in accomplishing catalysis. We will then present recent NMR data aimed at elucidating the key functional states associated with the adensoine A2A G-Protein-Coupled Receptor. The free-energy landscape is tremendously informative with regard to mechanistic explanations of activation and signal transduction and provides new opportunities for drug discovery.

J. Scott Prosser