化酶与半解离的S2B连接体的假定反应机制
1Department of Computational Chemistry, Lund University, Chemical Centre, P. O. Box 124, SE-221 00 Lund, Sweden. Ulf.Ryde@compchem.lu.se.
Dalton transactions (Cambridge, England : 2003)
|June 25, 2024
概括
在反应机制中,S2B硫化物联体与酶活性位点的解离通常是不利的. 这一发现表明S2B在后期阶段起到较小的作用,影响基质结合偏好.
科学领域:
- 生物化学和分子生物学
- 计算化学的计算化学
背景情况:
- 基酶催化固化,这是一个重要的生物过程.
- 在基酶机制中S2B硫化联体解离的作用尚未完全理解.
- 以前的模型假设S2B的完全解离或桥接.
研究的目的:
- 调查S2B硫化物联体的部分解离对化酶反应机制的影响.
- 探索质子化对S2B行为及其对基质结合的影响.
主要方法:
- 使用了量子力学和分子力学 (QM/MM) 的结合计算.
- 采用密度函数理论方法:r2SCAN和TPSSh.
- 模拟了反应机制,从E4状态开始与N2H2结合,并结合了质子化S2B.
主要成果:
- 在化酶反应的大部分步骤中,发现S2B的半解离是不利的.
- 只有当NH或NH2结合时才观察到有利的S2B半解离,桥梁Fe2和Fe6.
- 这些有利的状态可能不是主要反应途径的核心,或者是短暂的中间体.
结论:
- 在化酶反应机制的后期阶段,S2B配体的部分解离起到较小的作用.
- 一个质子化的S2B倾向于交替的基质质子化机制和结合Fe2.
- 这与无质子S2B形成鲜明对比,S2B有利于与Fe6.6结合.
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