Nonperfect synchronization of reaction center rehybridization in the transition state of the hydride transfer catalyzed by dihydrofolate reductase

A theoretical study designed to examine the reliability of inferring the transition state structure for an enzyme-catalyzed hydride transfer reaction on the basis of an empirical criterion is presented. Results reveal that the donor carbon at the hydride transfer transition state resembles the reactant state more than the product state, whereas the acceptor carbon is more productlike, which is a symptom of transition state imbalance.