Proton-coupled electron transfer in soybean lipoxygenase
Proton-coupled electron transfer in soybean lipoxygenase
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DOI：
10.1021/ja039606o
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发表时间：
2004-05-12
影响因子：
15
通讯作者：
Hammes-Schiffer, S
中科院分区：
文献类型：
--
作者：
Hatcher, E;Soudackov, AV;Hammes-Schiffer, S
利用一种多态连续体理论对大豆脂氧合酶 -1催化的质子耦合电子转移反应进行了研究，该理论将转移的氢核表示为量子力学波函数。利用密度泛函理论计算铁辅因子的内球重组能，利用对接模拟得到的构象通过频率分辨腔模型计算蛋白质的外球重组能。介绍了对质子供体 - 受体振动运动的经典和量子力学处理方法。计算速率和动力学同位素效应的温度依赖性与实验数据一致。速率对温度的弱依赖性是由于重组能和反应自由能之间的平衡导致自由能垒相对较小。异常高的氘动力学同位素效应（81）是由于反应物和产物质子振动波函数的重叠较小以及在隧穿过程中最低能量的反应物和产物电子振动态占主导地位。动力学同位素效应的温度依赖性受质子供体 - 受体距离的强烈影响，该距离对总速率起主要作用。这个主要的质子供体 - 受体距离明显小于平衡供体 - 受体距离，并且由距离减小时较大的耦合和较小的玻尔兹曼概率之间的平衡所决定。因此，质子供体 - 受体振动运动在使主要供体 - 受体距离相对于其平衡值减小以促进质子耦合电子转移反应方面起着至关重要的作用。
The proton-coupled electron transfer reaction catalyzed by soybean lipoxygenase-1 is studied with a multistate continuum theory that represents the transferring hydrogen nucleus as a quantum mechanical wave function. The inner-sphere reorganization energy of the iron cofactor is calculated with density functional theory, and the outer-sphere reorganization energy of the protein is calculated with the frequency-resolved cavity model for conformations obtained with docking simulations. 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 weak temperature dependence of the rates is due to the relatively small free energy barrier arising from a balance between the reorganization energy and the reaction free energy. The unusually high deuterium kinetic isotope effect of 81 is due to the small overlap of the reactant and product proton vibrational wave functions and the dominance of the lowest energy reactant and product vibronic states in the tunneling process. The temperature dependence of the kinetic isotope effect is strongly influenced by the proton donor-acceptor distance with the dominant contribution to the overall rate. This dominant proton donor-acceptor distance is significantly smaller than the equilibrium donor-acceptor distance and is determined by a balance between the larger coupling and the smaller Boltzmann probability as the distance decreases. Thus, the proton donor-acceptor vibrational motion plays a vital role in decreasing the dominant donor-acceptor distance relative to its equilibrium value to facilitate the proton-coupled electron transfer reaction.