Macromolecular structure and dynamics (Key words: NMR, Protein Folding)
Summary of Research:
Our laboratory is interested in elucidating the gamut of structural elements in a protein which control its function. For example glycolytic enzymes from parasitic protozoa are significantly different from mammalian homologues in their cellular role and regulation. The tertiary structures of Phosphoglycerate kinase from different organisms are very similar even though in some cases the sequence homology is no more than fifty percent. How can one then account for differences in substrate binding and catalysis? Proteins are not rigid balls but dynamic molecules that can bend, slide and reorient themselves. B-factor of residues in crystallographic structures as well as the rmsd of backbone and side-chains in solution structures are indicators of strong dynamic regions in a biomolecule. NMR methodology can be used effectively to look at protein microenvironments under different solution conditions. In principle movements on medium to slow scale can be trapped and studied by NMR. These lead to important clues to protein function.