Fundamental Insights into Proton-Coupled Electron Transfer in Soybean Lipoxygenase from Quantum Mechanical/Molecular Mechanical Free Energy Simulations.

ABSTRACT: The proton-coupled electron transfer (PCET) reaction catalyzed by soybean lipoxygenase has served as a prototype for understanding hydrogen tunneling in enzymes. Herein this PCET reaction is studied with mixed quantum mechanical/molecular mechanical (QM/MM) free energy simulations. The free energy surfaces are computed as functions of the proton donor-acceptor (C-O) distance and the proton coordinate, and the potential of mean force is computed as a function of the C-O distance, inherently including anharmonicity. The simulation results are used to calculate the kinetic isotope effects for the wild-type enzyme (WT) and the L546A/L754A double mutant (DM), which have been measured experimentally to be ∼80 and ∼700, respectively. The PCET reaction is found to be exoergic for WT and slightly e

SUBMITTER: Li P 

PROVIDER: S-EPMC5849423 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature