Department of Biochemistry, Instituto de Quı́mica, Universidade de São Paulo, Av. Prof. Lineu Prestes 748, 05508-900 São Paulo, SP, Brazil.
J Chem Inf Model. 2020 Dec 28;60(12):6282-6287. doi: 10.1021/acs.jcim.0c00945. Epub 2020 Nov 2.
Flavins are versatile biological cofactors which catalyze proton-coupled electron transfers (PCET) with varying number and coupling of electrons. Flavin-mediated oxidations of nicotinamide adenine dinucleotide (NADH) and of succinate, initial redox reactions in cellular respiration, were examined here with multiconfigurational quantum chemical calculations and a simple analysis of the wave function proposed to quantify electron transfer along the proton reaction coordinate. The mechanism of NADH oxidation is a prototypical hydride transfer, with two electrons moving concerted with the proton to the same acceptor group. However, succinate oxidation depends on the elimination step and can proceed through the transfer of a hydride or hydrogen atom, with proton and electrons moving to different groups in both cases. These results help to determine the mechanism of fundamental but still debated biochemical reactions and illustrate a new diagnostic tool for electron transfer that can be useful to characterize a broad class of PCET processes.
黄素是多功能的生物辅因子，可催化质子耦合电子转移（PCET），其电子数和耦合数各不相同。本文通过多组态量子化学计算和对波函数的简单分析，研究了黄素介导的烟酰胺腺嘌呤二核苷酸（NADH）和琥珀酸的氧化，波函数的分析用于沿质子反应坐标定量电子转移。NADH 氧化的机制是典型的氢化物转移，两个电子与质子协同移动到相同的受体基团。然而，琥珀酸氧化取决于消除步骤，可以通过氢化物或氢原子的转移进行，在这两种情况下，质子和电子都移动到不同的基团。这些结果有助于确定基本但仍有争议的生化反应的机制，并说明了一种新的电子转移诊断工具，可用于表征广泛的 PCET 过程。
