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Celia Schiffer, Ph.D.Academic Role: Professor
Faculty Appointment(s) In:
Other Affiliation(s):
In the maturation of the human immunodeficiency virus, HIV protease
specifically recognizes and cleaves nine non-homologous sites in the gag-pol
polyproteins. How this symmetric homodimeric protein is able to specifically
recognize not only a single substrate, but a variety of substrate sequences
poses fascinating questions of molecular recognition. What allows
one molecule to recognize, bind, cleave and release others? To elucidate
this specificity, our laboratory has solved for the first time structures
of substrate complexes of HIV protease with an inactive variant of HIV
protease. The complex with the peptide that releases the capsid
protein is shown above. These structures are then starting points
for molecular dynamics simulations to probe the conformational adaptability
of this protease, its substrates and the solvent environment. In
addition as drug resistant mutations occur the specificity of the protease
changes, we are elucidating these changes with phage display, enzyme kinetics
and crystal structures of drug resistant proteases bound to inhibitors.
Office: Research 923, Lab 970 L&M
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364 Plantation Street Worcester, MA 01605