Proton-coupled electron transfer reaction in soybean lipoxygenase

The proton-coupled electron transfer (PCET) reaction catalyzed by soybean lipoxygenase-1 is studied with a multistate continuum theory that represents the transferring hydrogen nucleus as a quantum mechanical wavefunction. Both classical and quantum mechanical treatments of the proton donor-acceptor vibrational motion are presented. The temperature dependence of the calculated rates and kinetic isotope effects is in agreement with the experimental data. The temperature dependence of the kinetic isotope effect is strongly influenced by the proton donor-acceptor distance. Thus, the proton donor-acceptor vibrational motion plays a vital role in facilitating the proton-coupled electron transfer reaction.;A general theoretical formulation for proton-coupled electron transfer reactions is presented. The solute is represented by a multistate valence bond model, and the active electrons and transferring proton(s) are treated quantum mechanically. This formulation enables the classical or quantum mechanical treatment of the proton donor-acceptor vibrational mode, as well as the dynamical treatment of the proton donor-acceptor mode and the solvent. Nonadiabatic rate expressions are presented for PCET reactions in a number of well-defined limits for both dielectric continuum and molecular representations of the environment. The dynamical rate expressions account for correlations between the fluctuations of the proton donor-acceptor distance and the nonadiabatic PCET coupling. The significance of the quantum and dynamical effects of the proton donor-acceptor mode is illustrated with applications to model PCET systems.;The dynamical aspects of a model proton-coupled electron transfer (PCET) reaction in solution are analyzed with molecular dynamics simulations. The rate constant for nonadiabatic PCET reactions is expressed in terms of a time-dependent probability flux correlation function. The impact of the proton donor-acceptor mode and solvent dynamics on the probability flux is examined. The analysis of PCET reactions is compared to previous analyses of single electron and proton transfer reactions.;Fundamental aspects of PCET reactions in solution are analyzed with molecular dynamics simulations for a series of model systems. The analysis addresses the impact of the solvent reorganization energy, the proton donor-acceptor mode vibrational frequency, and the distance dependence of the nonadiabatic coupling on the dynamics of the reaction and the magnitude of the rate. The approximations underlying a previously derived analytical PCET rate expression are also investigated.;The dynamical behavior and the temperature dependence of the kinetic isotope effects are examined for the PCET reaction catalyzed by the enzyme soybean lipoxygenase. The calculations are based on a vibronically nonadiabatic formulation that includes the quantum mechanical effects of the active electrons and the transferring proton, as well as the motions of all atoms in the complete solvated enzyme system. The calculations reproduce the experimentally observed magnitude and temperature dependence of the kinetic isotope effect for the soybean lipoxygenase reaction without fitting any parameters directly to the experimental kinetic data.