Puig Eduard, Garcia-Viloca Mireia, González-Lafont Angels, Lluch José M
Departament de Química, Universitat Autonoma de Barcelona, Bellaterra (Barcelona), Spain.
J Phys Chem A. 2006 Jan 19;110(2):717-25. doi: 10.1021/jp054555y.
Computer simulations on a QM/MM potential energy surface have been carried out to gain insights into the catalytic mechanism of glutamate racemase (MurI). Understanding such a mechanism is a challenging task from the chemical point of view because it involves the deprotonation of a low acidic proton by a relatively weak base to give a carbanionic intermediate. First, we have examined the dependency of the kinetics and thermodynamics of the racemization process catalyzed by MurI on the ionization state of the substrate (glutamate) main chain. Second, we have employed an energy decomposition procedure to study the medium effect on the enzyme-substrate electrostatic and polarization interactions along the reaction. Importantly, the present theoretical results quantitatively support the mechanistic proposal by Rios et al. [J. Am. Chem. Soc. 2000, 122, 9373-9385] for the PLP-independent amino acid racemases.
已在量子力学/分子力学势能面上进行了计算机模拟，以深入了解谷氨酸消旋酶（MurI）的催化机制。从化学角度来看，理解这样一种机制是一项具有挑战性的任务，因为它涉及到一个相对较弱的碱使一个低酸性质子去质子化，从而生成一个碳负离子中间体。首先，我们研究了MurI催化的消旋化过程的动力学和热力学对底物（谷氨酸）主链电离状态的依赖性。其次，我们采用了能量分解程序来研究反应过程中介质对酶-底物静电和极化相互作用的影响。重要的是，目前的理论结果定量地支持了里奥斯等人[《美国化学会志》2000年，122卷，9373 - 9385页]对不依赖磷酸吡哆醛的氨基酸消旋酶的机理提议。
