NgnD酶催化双峰环加成分叉为[6+4]-和[4+2]-加合物。两种产物都已在实验中分离出来,但在飞秒时间尺度上酶和水是如何影响分岔选择性的尚不清楚。
该文中,研究人员结合量子力学/分子力学准经典动力学模拟和生化分析,研究了水和酶对NgnD催化的[6+4]/[4+2]环加成反应过渡态后分岔的影响。[6+4]/[4+2]产物的比率在气相、水和酶中显著不同。生化分析用于验证计算预测。该研究通过在飞秒时间尺度上扰动反应动力学,揭示了水和酶如何影响分岔选择性,揭示了凝聚介质在动态控制生物合成反应化学选择性中的基本作用。
附:英文原文
Title: Influence of Water and Enzyme on the Post-Transition State Bifurcation of NgnD-Catalyzed Ambimodal [6+4]/[4+2] Cycloaddition
Author: Xin Wang, Chun Zhang, Yaoyukun Jiang, Wen Wang, Yuan Zhou, Yu Chen, Bo Zhang, Ren Xiang Tan, Hui Ming Ge, Zhongyue J. Yang, Yong Liang
Issue&Volume: December 1, 2021
Abstract: The enzyme NgnD catalyzes an ambimodal cycloaddition that bifurcates to [6+4]- and [4+2]-adducts. Both products have been isolated in experiments, but it remains unknown how enzyme and water influence the bifurcation selectivity at the femtosecond time scale. Here, we study the impact of water and enzyme on the post-transition state bifurcation of NgnD-catalyzed [6+4]/[4+2] cycloaddition by integrating quantum mechanics/molecular mechanics quasiclassical dynamics simulations and biochemical assays. The ratio of [6+4]/[4+2] products significantly differs in the gas phase, water, and enzyme. Biochemical assays were employed to validate computational predictions. The study informs how water and enzyme affect the bifurcation selectivity through perturbation of the reaction dynamics in the femtosecond time scale, revealing the fundamental roles of condensed media in dynamically controlling the chemical selectivity for biosynthetic reactions.
DOI: 10.1021/jacs.1c10760
Source: https://pubs.acs.org/doi/10.1021/jacs.1c10760
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