Prat-Resina Xavier, Gonzalez-Lafont Angels, Lluch José M
Departament de Química, Universitat Autonoma de Barcelona, 08193 Bellaterra (Barcelona), Spain.
J Phys Chem B. 2005 Nov 10;109(44):21089-101. doi: 10.1021/jp052239d.
The present work studies the reaction mechanism of the racemization of mandelate substrate by mandelate racemase enzyme. The reaction has some intriguing aspects such as the deprotonation of a nonacid hydrogen and the achievement of the pseudosymmetry necessary to obtain the racemic mixture. We will make use of a QM/MM potential energy surface to compute the free energy profiles associated with the reaction. The most favorable reaction mechanism consists of two proton transfers and the configuration inversion of the stereogenic carbon taking place in a concerted manner. We have also designed a suitable reaction coordinate to compute the free energy profiles for this rather complicated reaction. In addition, analysis of the electrostatic effects and bond distances along the reaction will explain how the enzyme accomplishes the catalysis. Finally, the enzymatic reaction will be compared to a model of the uncatalyzed reaction and the catalytic effect of mandelate racemase will be evaluated.
本研究工作探究了扁桃酸消旋酶催化扁桃酸底物外消旋化的反应机理。该反应具有一些有趣的方面，比如非酸性氢的去质子化以及获得外消旋混合物所需的假对称性的实现。我们将利用量子力学/分子力学势能面来计算与该反应相关的自由能曲线。最有利的反应机理包括两个质子转移以及手性碳的构型翻转，它们以协同方式发生。我们还设计了一个合适的反应坐标来计算这个相当复杂反应的自由能曲线。此外，对反应过程中静电效应和键长的分析将解释酶是如何实现催化作用的。最后，将酶促反应与无催化反应模型进行比较，并评估扁桃酸消旋酶的催化效果。
