With this award, the Chemistry of Life Processes Program in the Chemistry Division is funding Dr. Elan Eisenmesser from the University of Colorado Denver to investigate how motions within an enzyme communicate to control enzyme function. With the development of technological methods capable of identifying the positions of all the atoms in molecules over the last two decades, it has become increasingly clear that macromolecules, and particularly enzymes, are reliant on a range of motions for their functions. However, how these motions are communicated across an enzyme in order to control their functions is less understood. Utilizing newly developed techniques that bridge molecular biology and nuclear magnetic resonance, graduate and undergraduate students will reveal how motions on multiple timescales communicate within a critical biological enzyme, called Bilirubin Reductase B, and whether there is cross-talk between movements on different timescales. Such studies could impact efforts to engineer enzymes by considering both their structure and intrinsic motions. Dr. Eisenmesser also plans to introduce these studies to minority undergraduates in order to train students in molecular biology and state-of-the-art biophysical techniques that probe the atomic level details of both structure and motions.
The research project is aimed at elucidating how networks of coupled motions regulate active site dynamics and how these in turn modulate catalytic turnover. Dynamic communication is now well understood to play critical roles in enzyme function and many recent studies have shown that motions are only partially correlated. Thus, identifying the molecular basis of these partial couplings and specifically modulating distal dynamics in order to control enzyme function will significantly impact efforts for enzyme engineering.
This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.
