Faculty of Chemistry, Jagiellonian University, 30-387 Kraków, Poland.
National Institute of Chemistry, SI-1000 Ljubljana, Slovenia.
Molecules. 2019 Nov 28;24(23):4359. doi: 10.3390/molecules24234359.
Monoamine oxidase A (MAO A) is a well-known enzyme responsible for the oxidative deamination of several important monoaminergic neurotransmitters. The rate-limiting step of amine decomposition is hydride anion transfer from the substrate α-CH2 group to the N5 atom of the flavin cofactor moiety. In this work, we focus on MAO A-catalyzed benzylamine decomposition in order to elucidate nuclear quantum effects through the calculation of the hydrogen/deuterium (H/D) kinetic isotope effect. The rate-limiting step of the reaction was simulated using a multiscale approach at the empirical valence bond (EVB) level. We applied path integral quantization using the quantum classical path method (QCP) for the substrate benzylamine as well as the MAO cofactor flavin adenine dinucleotide. The calculated H/D kinetic isotope effect of 6.5 ± 1.4 is in reasonable agreement with the available experimental values.
单胺氧化酶 A（MAO A）是一种众所周知的酶，负责氧化脱氨几种重要的单胺能神经递质。胺分解的限速步骤是从底物α-CH2 基团向黄素辅因子部分的 N5 原子转移氢阴离子。在这项工作中，我们专注于 MAO A 催化的苄胺分解，以通过计算氢/氘（H/D）动力学同位素效应来阐明核量子效应。使用经验价键（EVB）水平的多尺度方法模拟了反应的限速步骤。我们应用量子经典路径法（QCP）对底物苄胺和 MAO 辅因子黄素腺嘌呤二核苷酸进行路径积分量子化。计算得到的 H/D 动力学同位素效应为 6.5±1.4，与现有实验值吻合较好。
