 |
 |
SCIENCE AT THE EDGE SEMINAR
QB/GEDD
Friday, March 25 at 11:30am
Room 1400 Biomedical and Physical Sciences Bldg.
Refreshments at 11:15
Gail Fanucci
Department of Chemistry, University of Florida, Gainesville, FL
Probing Effects of Amino Acid Substitutions on HIV-1 Protease Conformational Flexibility with Pulsed EPR Spectroscopy
We have recently shown that conformational sampling in HIV-1 protease (HIV-1PR) can be captured with site-directed spin labeling (SDSL) and pulsed electron paramagnetic resonance (EPR) methods. Specifically
a nitroxide spin-label is incorporated into the flap region of the protease. By combing results from experimental distance measurements with molecular dynamic simulations models regarding four predominant conformational states are seen, and the relative population
of these states is modulated by amino acid substitutions. Results for select natural polymorphism subtypes, drug pressure selected mutations and co-evolved non-active site mutations will be presented and discussed. Results demonstrate that mutations distal
from the active site that modulate enzymatic activity have a dramatic effect on the relative populations of the conformational states. We are in the process of correlating changes in conformational sampling with enzymatic activity.
Helen Geiger
Administrative Assistant
Quantitative Biology Graduate Program/
Gene Expression in Development & Disease
Michigan State University
502B Biochemistry Building
East Lansing, MI 48824
Phone: (517) 432-9895
Fax: (517) 353-9334
Web: http://qbmi.msu.edu
http://www.bch.msu.edu/GEDD/index.htm