Extension and limits of the network of coupled motions correlated to hydride transfer in dihydrofolate reductase.

ABSTRACT: Enzyme catalysis has been studied extensively, but the role of enzyme dynamics in the catalyzed chemical conversion is still an enigma. The enzyme dihydrofolate reductase (DHFR) is often used as a model system to assess a network of coupled motions across the protein that may affect the catalyzed chemical transformation. Molecular dynamics simulations, quantum mechanical/molecular mechanical studies, and bioinformatics studies have suggested the presence of a "global dynamic network" of residues in DHFR. Earlier studies of two DHFR distal mutants, G121V and M42W, indicated that these residues affect the chemical step synergistically. While this finding was in accordance with the concept of a network of functional motions across the protein, two residues do not constitute a network. To bett

SUBMITTER: Singh P 

PROVIDER: S-EPMC3985941 | biostudies-literature | 2014 Feb

REPOSITORIES: biostudies-literature