Teh Pat Flexibility of proteins is an integral part of their function. This motion can include reorganization of catalytic groups, loop closures, and domain movement, to name a few. The focus of our research is to understand how the dynamic and structural properties of proteins correlate with their function. The general questions that we would like to address are:

Our primary experimental tool for approaching these questions is nuclear magnetic resonance (NMR) spectroscopy. NMR is the only experimental technique that can access molecular motion on time scales from 10-12 - 101 seconds. Historically, detailed NMR studies have been restricted to peptides and small proteins. However recent advances in the field have allowed for in-depth studies of larger proteins, opening up this technique to a broad range of interesting protein dynamics questions.

A detailed understanding of the link between enzyme flexibility and function is crucial for protein engineering, protein and drug design and for obtaining a physical chemical understanding of enzyme function. Our lab utilizes many biophysical techniques with a focus on solution NMR spectroscopy to characterize conformational motions in functional enzymes. Currently, our interest center on the relationship between active site loop closure in protein tyrosine phosphatases (YopH, PTP1B, and VHR) and their catalytic activity and whether allosteric ligand can modulate loop motions. In the enzyme imidazole glycerol phosphate synthase we are searching for a mechanistic understanding of allosteric information transfer that spans tens of Angstroms. Whereas in DNA Polymerase beta (Polb) we are trying to illuminate the role of protein flexibility on substrate fidelity and its role in cancer causing mutants of Polb.





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