Roca Maite, Andrés Juan, Moliner Vicent, Tuñón Iñaki, Bertrán Juan
Departament de Ciències Experimentals, Universitat Jaume I, 12071 Castellón, Spain.
J Am Chem Soc. 2005 Aug 3;127(30):10648-55. doi: 10.1021/ja051503d.
The way in which enzymes influence the rate of chemical processes is still a question of debate. The protein promotes the catalysis of biochemical processes by lowering the free energy barrier in comparison with the reference uncatalyzed reaction in solution. In this article we are reporting static and dynamic aspects of the enzyme catalysis in a bimolecular reaction, namely a methyl transfer from S-adenosylmethionine to the hydroxylate oxygen of a substituted catechol catalyzed by catechol O-methyltransferase. From QM/MM optimizations, we will first analyze the participation of the environment on the transition vector. The study of molecular dynamics trajectories will allow us to estimate the transmission coefficient from a previously localized transition state as the maximum in the potential of mean force profile. The analysis of the reactive and nonreactive trajectories in the enzyme environment and in solution will also allow studying the geometrical and electronic changes, with special attention to the chemical system movements and the coupling with the environment. The main result, coming from both analyses, is the approximation of the magnesium cation to the nucleophilic and the hydroxyl group of the catecholate as a result of a general movement of the protein, stabilizing in this way the transition state. Consequently, the free energy barrier of the enzyme reaction is dramatically decreased with respect to the reaction in solution.
酶影响化学过程速率的方式仍是一个有争议的问题。与溶液中未催化的参考反应相比，该蛋白质通过降低自由能垒来促进生化过程的催化作用。在本文中，我们报告了双分子反应中酶催化的静态和动态方面，即由儿茶酚O -甲基转移酶催化的从S -腺苷甲硫氨酸到取代儿茶酚羟基氧的甲基转移。通过量子力学/分子力学（QM/MM）优化，我们将首先分析环境对过渡向量的参与情况。分子动力学轨迹的研究将使我们能够从先前定位的过渡态估计传输系数，该过渡态为平均力势轮廓中的最大值。对酶环境和溶液中反应性和非反应性轨迹的分析还将允许研究几何和电子变化，特别关注化学体系的运动以及与环境的耦合。来自这两种分析的主要结果是，由于蛋白质的整体运动，镁阳离子接近儿茶酚盐的亲核基团和羟基，从而以这种方式稳定过渡态。因此，相对于溶液中的反应，酶反应的自由能垒显著降低。
