The Chemistry of Life Processes Program in the Chemistry Division funds this research. Professors Amnon Kohen and Christopher Cheatum at the University of Iowa investigate how enzymes accelerate chemical reactions. Enzymes are protein molecules. They are large and dynamic, and vibrate very fast. The research seeks to find out if specific vibrations of the protein contribute to the extraordinary rate accelerations of the enzyme-catalyzed reactions. The investigators devise new molecular tools that make it possible to measure fast vibrations in specific places in the enzyme. Comparing the changes in the reactants with the changes in the motions of the protein reveal the role that protein's motions play in the reactivity. This research gives graduate and undergraduate students specialized training in a diverse and unique scientific skill set. The outreach activities have a demonstrated record of engaging high school students in basic science and steering some toward studies and careers in science. These activities enhance scientific awareness for other students who are not interested in scientific careers.
This research project identifies correlations between enzyme dynamics and chemical reactivity of carbon-hydrogen carbon (C-H C) transfer reactions. The role of networks of coupled motions of the protein in modulating that relationship in dihydrofolate reductase is also examined. The effects of both active-site and distal mutations on the chemical step by the temperature dependence of the primary kinetic isotope effects (KIEs) and on the protein dynamics by two-dimensional infrared (2D IR) spectroscopy are measured. Mutants that have previously been studied using KIEs that suggest a role for enzyme motions in the catalyzed reaction are used for the combined spectroscopic and kinetic studies. Differences between the human and E. coli enzymes are assessed and compared to theoretical predictions for these two related enzymes. This research gives graduate and undergraduate students specialized training in a diverse and unique scientific skill set. The combination of methods may be quite general and apply to a range of enzymes. This project is integrated with an outreach effort to communicate this science to the public.
