Proton-Coupled Electron Transfer in Soybean Lipoxygenase: Dynamical Behavior and Temperature Dependence of Kinetic Isotope Effects

详细信息    查看全文

• 作者：Elizabeth Hatcher ; Alexander V. Soudackov ; Sharon Hammes-Schiffer
• 刊名：Journal of the American Chemical Society
• 出版年：2007
• 出版时间：January 10, 2007
• 年：2007
• 卷：129
• 期：1
• 页码：187 - 196
• 全文大小：190K
• 年卷期：v.129,no.1(January 10, 2007)
• ISSN：1520-5126

文摘

The dynamical behavior and the temperature dependence of the kinetic isotope effects (KIEs)are examined for the proton-coupled electron transfer reaction catalyzed by the enzyme soybeanlipoxygenase. The calculations are based on a vibronically nonadiabatic formulation that includes thequantum mechanical effects of the active electrons and the transferring proton, as well as the motions ofall atoms in the complete solvated enzyme system. The rate constant is represented by the time integralof a probability flux correlation function that depends on the vibronic coupling and on time correlation functionsof the energy gap and the proton donor-acceptor mode, which can be calculated from classical moleculardynamics simulations of the entire system. The dynamical behavior of the probability flux correlation functionis dominated by the equilibrium protein and solvent motions and is not significantly influenced by the protondonor-acceptor motion. The magnitude of the overall rate is strongly influenced by the proton donor-acceptor frequency, the vibronic coupling, and the protein/solvent reorganization energy. The calculationsreproduce the experimentally observed magnitude and temperature dependence of the KIE for the soybeanlipoxygenase reaction without fitting any parameters directly to the experimental kinetic data. The temperaturedependence of the KIE is determined predominantly by the proton donor-acceptor frequency and thedistance dependence of the vibronic couplings for hydrogen and deuterium. The ratio of the overlaps ofthe hydrogen and deuterium vibrational wavefunctions strongly impacts the magnitude of the KIE but doesnot significantly influence its temperature dependence. For this enzyme reaction, the large magnitude ofthe KIE arises mainly from the dominance of tunneling between the ground vibronic states and the relativelylarge ratio of the overlaps between the corresponding hydrogen and deuterium vibrational wavefunctions.The weak temperature dependence of the KIE is due in part to the dominance of the local component ofthe proton donor-acceptor motion.