Changes in protein architecture and subpicosecond protein dynamics impact the reaction catalyzed by lactate dehydrogenase.

ABSTRACT: We have previously established the importance of a promoting vibration, a subpicosecond protein motion that propagates through a specific axis of residues, in the reaction coordinate of lactate dehydrogenase (LDH). To test the effect that perturbation of this motion would have on the enzymatic reaction, we employ transition path sampling to obtain transition path ensembles for four independent LDH enzymatic systems: the wild type enzyme, a version of the enzyme expressing heavy isotopic substitution, and two enzymes with mutations in the promoting vibration axis. We show that even slight changes in the promoting vibration of LDH result in dramatic changes in enzymatic chemistry. In the "heavy" version of the enzyme, we find that the dampening of the subpicosecond dynamics from heavy isotop

SUBMITTER: Masterson JE 

PROVIDER: S-EPMC3695017 | biostudies-literature | 2013 Aug

REPOSITORIES: biostudies-literature