Small temperature dependence of the kinetic isotope effect for the hydride transfer reaction catalyzed by Escherichia coli dihydrofolate reductase.
Small temperature dependence of the kinetic isotope effect for the hydride transfer reaction catalyzed by Escherichia coli dihydrofolate reductase.
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DOI：
10.1021/jp051184c
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发表时间：
2005-05
期刊：
影响因子：
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通讯作者：
J. Pu;Shuhua Ma;Jiali Gao;D. Truhlar
中科院分区：
文献类型：
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作者：
J. Pu;Shuhua Ma;Jiali Gao;D. Truhlar
采用多维隧道理论计算了大肠杆菌二氢叶酸还原酶（ecDHFR）催化氢化物转移反应的H/D初级动力学同位素效应（KIE）。在5 ~ 45℃的温度范围内，计算出的KIE仅显示出很小的温度依赖性。我们确定了两个关键特征，它们有助于消除基于更简单模型所期望的KIE的大部分温度依赖性。讨论了同位素对Arrhenius指数前因子的影响、活化能自由能与Arrhenius活化能之间的较大差异以及有效势垒的波动等问题。
The H/D primary kinetic isotope effect (KIE) for the hydride transfer reaction catalyzed by Escherichia coli dihydrofolate reductase (ecDHFR) is calculated as a function of temperature employing ensemble-averaged variational transition-state theory with multidimensional tunneling. The calculated KIEs display only a small temperature dependence over the temperature range of 5 to 45 degrees C. We identify two key features that contribute to canceling most of the temperature dependence of the KIE that would be expected on the basis of simpler models. Related issues such as the isotope effects on Arrhenius preexponential factors, large differences between free energies of activation and Arrhenius activation energy, and fluctuations of effective barriers are also discussed.