Patrick Wintrode
Assistant Professor
Protein folding, dynamics and regulation
RESEARCH DESCRIPTION
Research in our lab focuses on macromolecular structure, dynamics and interactions using hydrogen/deuterium exchange and mass spectrometry.
One major project in our lab involves using hydrogen exchange and mass spectrometry to study the conformational properties of serpins, an important class of protease inhibitors. Unlike most proteins, serpins fold to a metastable state, and this metastability is intimately related to their function. We are using hydrogen exchange to determine the distribution of conformational fluctuations and thermodynamic stability in the serpin molecule. This information is important in understanding how serpins achieve the large scale structural changes that are required as part of their biological function. We are also mapping the serpin folding pathway in order to understand how serpins are able fold to a metastable, rather than a globally stable, conformation. In addition to its interest for fundamental protein folding research, the folding pathway of serpins is of medical importance since a number of diseases, including liver cirrhosis and emphysema, have been linked to the improper folding of serpins.
A second project is focused on the dynamics and assembly of HIV-1 reverse transcriptase. Reverse transcriptase is a critical enzyme in the maturation of HIV and a popular target for drug design. The first stage of assembly involves the dimerization of two identical 66kD subunits, which are subsequently processed to give the mature heterodimer of one 66kD and one 51kD subunit. We are using hydrogen exchange to investigate the structures of intermediates in this process, particularly the 66/66 kD homodimer. We are also investigating the effect of inhibitors on the dynamics of HIV reverse transcriptase. By examining the effects of inhibitor binding on wild type and drug resistant mutants of reverse transcriptase, we hope to shed light on the mechanism of inhibition and the physical basis of drug resistance.
RELATED RESEARCH AREAS
View Patrick Wintrode's Publications on PubMed
|
 |
Cleveland, Ohio 44106-4970 
