Perry A. Frey

The central thrust of my research is the elucidation of the mechanisms of enzymatic reactions. Two aspects are of particular interest. First is the question of how enzymes use binding interactions directed to remote parts of substrate molecules to decrease activation energies. The role of strong hydrogen bonds and electrostatic interactions are of particular interest. The second focus of my research is the elucidation of the mechanisms of enzymatic reactions that are obscure in chemical terms and for which no obvious chemical precedent is available. These enzymes generally function by radical mechanisms. Lysine 2,3-aminomutase, one example of such an enzyme, is a major subject of current research in this field. The required cofactors include pyridoxal-5'-phosphate, S-adenosylmethionine, and an iron-sulfur cluster. The cofactors all function by biologically and chemically novel mechanisms unlike those characteristic of the same cofactors in other biological reactions. They are under intensive investigation by biochemical, genetic, spectroscopic, kinetic, and structural methods.