Hydrogen tunnelling in enzyme-catalysed H-transfer reactions: flavoprotein and quinoprotein systems
Hydrogen tunnelling in enzyme-catalysed H-transfer reactions: flavoprotein and quinoprotein systems
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DOI：
10.1098/rstb.2006.1878
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发表时间：
2006-08-29
影响因子：
6.3
通讯作者：
Scrutton, Nigel S.
中科院分区：
文献类型：
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作者：
Sutcliffe, Michael J.;Masgrau, Laura;Scrutton, Nigel S.
现在广泛接受的是，酶催化的C-H键断裂通过量子力学隧道效应发生。这些反应的概念框架从半经典过渡态理论的范式转变（TST，即包括零点能，但没有隧道效应校正）近年来一直受到一系列酶中这些反应的动力学同位素效应（KIE）的温度依赖性的实验研究的驱动，包括色氨酸对甲萘醌依赖性酶如甲胺脱氢酶和芳香胺脱氢酶，和黄素酶如吗啡酮还原酶和季戊四醇四硝酸酯还原酶，这产生的观测结果也与简单的贝尔修正隧道模型不一致。然而，这些数据-特别是，强烈的温度依赖性的反应速率和可变的温度依赖性的KIEs-是一致的与其他隧道模型（称为全隧道模型），其中蛋白质和/或底物的波动产生的配置与隧道兼容。这些模型适应基板/蛋白质（环境）的波动，需要达到一个配置与简并核量子态，并在必要时，运动需要增加在这些国家的隧穿的概率。此外，隧道机制在酶的支持下进行的现代TST，其中包括量子核效应的框架内的原子计算研究。
It is now widely accepted that enzyme-catalysed C-H bond breakage occurs by quantum mechanical tunnelling. This paradigm shift in the conceptual framework for these reactions away from semiclassical transition state theory (TST, i.e. including zero-point energy, but with no tunnelling correction) has been driven over the recent years by experimental studies of the temperature dependence of kinetic isotope effects (KIEs) for these reactions in a range of enzymes, including the tryptophan tryptophylquinone-dependent enzymes such as methylamine dehydrogenase and aromatic amine dehydrogenase, and the flavoenzymes such as morphinone reductase and pentaerythritol tetranitrate reductase, which produced observations that are also inconsistent with the simple Bell-correction model of tunnelling. However, these data-especially, the strong temperature dependence of reaction rates and the variable temperature dependence of KIEs-are consistent with other tunnelling models (termed full tunnelling models), in which protein and/or substrate fluctuations generate a configuration compatible with tunnelling. These models accommodate substrate/protein (environment) fluctuations required to attain a configuration with degenerate nuclear quantum states and, when necessary, motion required to increase the probability of tunnelling in these states. Furthermore, tunnelling mechanisms in enzymes are supported by atomistic computational studies performed within the framework of modern TST, which incorporates quantum nuclear effects.