The enzyme aromatic amine dehydrogenase induces a substrate conformation crucial for promoting vibration that significantly reduces the effective potential energy barrier to proton transfer
The enzyme aromatic amine dehydrogenase induces a substrate conformation crucial for promoting vibration that significantly reduces the effective potential energy barrier to proton transfer
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DOI：
10.1098/rsif.2008.0068.focus
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发表时间：
2008-12-06
影响因子：
3.9
通讯作者：
Sutcliffe, Michael J.
中科院分区：
文献类型：
--
作者：
Johannissen, Linus O.;Scrutton, Nigel S.;Sutcliffe, Michael J.
在涉及氢隧穿的酶反应中促进振动的作用是有争议的。虽然包含这种促进振动的模型已经成功地再现和解释了实验观察结果，但也有人认为这种振动不是催化效应的一部分。在这项研究中，我们采用了结合量子力学/分子力学方法与分子动力学和势能面计算，研究酶和底物运动如何影响质子转移的能量障碍的限速H-转移芳香胺脱氢酶（AADH）与色胺为底物的步骤。特别是，由AADH诱导的亚氨基醌加合物的构象被发现是必不可少的促进振动先前确定的，这显著降低了“有效”的势能势垒，这是障碍，仍然要克服以下集体，热平衡运动达到量子简并态的反应物和产物。当基板采用的构象类似于在游离亚氨基醌，这种障碍被发现显着增加。这与AADH通过将底物保持在诱导促进振动的构象中来促进H-转移事件是一致的。
The role of promoting vibrations in enzymic reactions involving hydrogen tunnelling is contentious. While models incorporating such promoting vibrations have successfully reproduced and explained experimental observations, it has also been argued that such vibrations are not part of the catalytic effect. In this study, we have employed combined quantum mechanical/molecular mechanical methods with molecular dynamics and potential energy surface calculations to investigate how enzyme and substrate motion affects the energy barrier to proton transfer for the rate-limiting H-transfer step in aromatic amine dehydrogenase (AADH) with tryptamine as substrate. In particular, the conformation of the iminoquinone adduct induced by AADH was found to be essential for a promoting vibration identified previously this lowers significantly the 'effective' potential energy barrier, that is the barrier which remains to be surmounted following collective, thermally equilibrated motion attaining a quantum degenerate state of reactants and products. When the substrate adopts a conformation similar to that in the free iminoquinone, this barrier was found to increase markedly. This is consistent with AADH facilitating the H-transfer event by holding the substrate in a conformation that induces a promoting vibration.