Our research is directed toward elucidation of the active site structures and catalytic mechanisms of enzymes involved in nucleoside metabolism. Enzymes presently under study include S-adenosylmethionine synthetase (ATP: L-methionine S-adenosyltransferase) which catalyzes formation of the primary biological alkylating agent, and inosine monophosphate dehydrogenase which catalyzes the rate limiting step in guanine nucleoside biosynthesis. These enzymes are recognized targets for chemotheraputic agents, and the availability of structural and mechanistic information promises the ability to develop new inhibitors through rational drug design methods. The research utilizes a multi-faceted approach that encompasses kinetic and spectroscopic studies of natural and designed mutant enzymes, and computational studies of the structures and energies of molecular interactions.