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Coordinated Effects Of Distal Mutations On Environmentally Coupled Tunneling In Dihydrofolate Reductase, Lin Wang, Nina M. Goodey, Stephen J. Benkovic, Amnon Kohen

Department of Chemistry and Biochemistry Faculty Scholarship and Creative Works

One of the most intriguing questions in modern enzymology is whether enzyme dynamics evolved to enhance the catalyzed chemical transformation. In this study, dihydrofolate reductase, a small monomeric protein that catalyzes a single C-H-C transfer, is used as a model system to address this question. Experimental and computational studies have proposed a dynamic network that includes two residues remote from the active site (G121 and M42). The current study compares the nature of the H-transfer step of the WT enzyme, two single mutants, and their double mutant. The contribution of quantum mechanical tunneling and enzyme dynamics to the H-transfer step …