Department of Mathematics, Huxley Building, Imperial College, London SW7 2AZ, United Kingdom.
CEMPS, Physics and Astronomy, University of Exeter, Exeter EX4 4QL, United Kingdom.
J Chem Phys. 2017 Sep 21;147(11):114108. doi: 10.1063/1.4998941.
The hydrogen transfer reaction catalysed by soybean lipoxygenase (SLO) has been the focus of intense study following observations of a high kinetic isotope effect (KIE). Today high KIEs are generally thought to indicate departure from classical rate theory and are seen as a strong signature of tunnelling of the transferring particle, hydrogen or one of its isotopes, through the reaction energy barrier. In this paper, we build a qualitative quantum rate model with few free parameters that describes the dynamics of the transferring particle when it is exposed to energetic potentials exerted by the donor and the acceptor. The enzyme's impact on the dynamics is modelled by an additional energetic term, an oscillatory contribution known as "gating." By varying two key parameters, the gating frequency and the mean donor-acceptor separation, the model is able to reproduce well the KIE data for SLO wild-type and a variety of SLO mutants over the experimentally accessible temperature range. While SLO-specific constants have been considered here, it is possible to adapt these for other enzymes.
大豆脂氧合酶（SLO）催化的氢转移反应一直是研究的焦点，这是因为观察到了高动力学同位素效应（KIE）。如今，高 KIE 通常被认为偏离了经典速率理论，并且被视为转移粒子（氢或其同位素之一）通过反应能垒隧穿的强烈特征。在本文中，我们构建了一个具有少数自由参数的定性量子速率模型，该模型描述了当转移粒子暴露于供体和受体施加的能量势时的动力学。通过一个附加的能量项，即所谓的“门控”的振荡贡献，来模拟酶对动力学的影响。通过改变两个关键参数，门控频率和平均供体-受体分离，该模型能够很好地再现 SLO 野生型和各种 SLO 突变体在实验可及温度范围内的 KIE 数据。虽然这里考虑了 SLO 特异性常数，但可以为其他酶改编这些常数。
