Evidence for Environmentally Coupled Hydrogen Tunneling during Dihydrofolate Reductase Catalysis
- 14 October 2003
- journal article
- research article
- Published by American Chemical Society (ACS) in Journal of the American Chemical Society
- Vol. 125 (44) , 13372-13373
- https://doi.org/10.1021/ja035692g
Abstract
Hydride transfer during catalysis by dihydrofolate reductase from Thermotoga maritima has been studied by stopped flow spectroscopy. The reduction of dihydrofolate by NADPH showed a biphasic temperature dependence of the deuterium kinetic isotope effect. At temperatures above 25 °C the KIE was temperature independent, while the reaction rates were strongly temperature dependent. Below 25 °C the KIE becomes dependent on temperature, and the ratio of the preexponential factors is inverse, suggesting a greater role for active dynamics that modulate the tunneling distance.Keywords
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