Probing the Transition State in Enzyme Catalysis by High-Pressure NMR Dynamics.

ABSTRACT: Protein conformational changes are frequently essential for enzyme catalysis, and in several cases, shown to be the limiting factor for overall catalytic speed. However, a structural understanding of corresponding transition states, needed to rationalize the kinetics, remains obscure due to their fleeting nature. Here, we determine the transition-state ensemble of the rate-limiting conformational transition in the enzyme adenylate kinase, by a synergistic approach between experimental high-pressure NMR relaxation during catalysis and molecular dynamics simulations. By comparing homologous kinases evolved under ambient or high pressure in the deep-sea, we detail transition state ensembles that differ in solvation as directly measured by the pressure dependence of catalysis. Capturing transi

SUBMITTER: Stiller JB 

PROVIDER: S-EPMC7063682 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature