Experimental and theoretical studies of enzyme-catalyzed hydrogen-transfer reactions

Abstract

The mechanisms of enzyme-catalyzed reactions are medicinally important and present a fascinating intellectual challenge. Many experimental and theoretical techniques can shed light on these mechanisms, and here, we shall focus on the utility of kinetic isotope effects (KIEs) to study enzymatic reactions that involve hydrogen transfers. We will provide a short background on the prevailing models to interpret KIEs and then present more detailed reviews of two model enzymes: alcohol dehydrogenase and thymidylate synthase. These two examples provide a context to describe the types of experiments and theoretical calculations that drive this field forward and the kind of information each can furnish. We emphasize the importance of cooperation between experimentalists and theoreticians to continue the progress toward a comprehensive theory of enzyme catalysis.