Catalysis by dihydrofolate reductase and other enzymes arises from electrostatic preorganization, not conformational motions.

ABSTRACT: The proposal that enzymatic catalysis is due to conformational fluctuations has been previously promoted by means of indirect considerations. However, recent works have focused on cases where the relevant motions have components toward distinct conformational regions, whose population could be manipulated by mutations. In particular, a recent work has claimed to provide direct experimental evidence for a dynamical contribution to catalysis in dihydrofolate reductase, where blocking a relevant conformational coordinate was related to the suppression of the motion toward the occluded conformation. The present work utilizes computer simulations to elucidate the true molecular basis for the experimentally observed effect. We start by reproducing the trend in the measured change in catalysis up

SUBMITTER: Adamczyk AJ 

PROVIDER: S-EPMC3161549 | biostudies-literature | 2011 Aug

REPOSITORIES: biostudies-literature