Strajbl Marek, Shurki Avital, Kato Mitsunori, Warshel Arieh
Department of Chemistry, University of Southern California, Los Angeles, California 90098-1062, USA.
J Am Chem Soc. 2003 Aug 27;125(34):10228-37. doi: 10.1021/ja0356481.
The catalytic reaction of chorismate mutase (CM) has been the subject of major current attention. Nevertheless, the origin of the catalytic power of CM remains an open question. In particular, it has not been clear whether the enzyme works by providing electrostatic transition state stabilization (TSS), by applying steric strain, or by populating near attack conformation (NAC). The present work explores this issue by a systematic quantitative analysis. The overall catalytic effect is reproduced by the empirical valence bond (EVB) method. In addition, the binding free energy of the ground state and the transition state is evaluated, demonstrating that the enzyme works by TSS. Furthermore, the evaluation of the electrostatic contribution to the reduction of the activation energy establishes that the TSS results from electrostatic effects. It is also found that the apparent NAC effect is not the reason for the catalytic effect but the result of the TSS. It is concluded that in CM as in other enzymes the key catalytic effect is electrostatic TSS. However, since the charge distribution of the transition state and the reactant state is similar, the stabilization of the transition state leads to reduction in the distance between the reacting atoms in the reactant state.
分支酸变位酶（CM）的催化反应是当前主要关注的课题。然而，CM催化能力的起源仍然是一个悬而未决的问题。特别是，目前尚不清楚该酶是通过提供静电过渡态稳定化（TSS）、施加空间应变还是通过形成近攻击构象（NAC）来发挥作用。本研究通过系统的定量分析来探讨这个问题。通过经验价键（EVB）方法再现了整体催化效果。此外，评估了基态和过渡态的结合自由能，表明该酶通过TSS发挥作用。此外，对静电对活化能降低的贡献的评估确定了TSS是由静电效应引起的。还发现明显的NAC效应不是催化作用的原因，而是TSS的结果。得出的结论是，与其他酶一样，在CM中关键的催化作用是静电TSS。然而，由于过渡态和反应物态的电荷分布相似，过渡态的稳定导致反应物态中反应原子之间距离的减小。
