人类二氧化碳无水酶II和IX的催化域的pH依赖结构和动力学
Divya Rai1, Dulal Mondal1, Srabani Taraphder1
1Department of Chemistry, Indian Institute of Technology Kharagpur, Kharagpur 721302, India.
The journal of physical chemistry. B
|November 20, 2023
概括
计算机模拟显示pH值影响人类碳酸酶 (HCA) 活性部位的动态,而不是结构. 这是一架His-64质子航天飞机.
科学领域:
- 生物化学 生物化学
- 计算化学计算化学
- 酶学 是一种酶学.
背景情况:
- 人类碳酸无水酶 (HCA) 是关键的金属酶,可催化CO2的可逆化和HCO3-的脱水.
- 异酶II和IX是人体内pH稳态的关键参与者.
- 了解它们的pH依赖性行为对于生理和治疗见解至关重要.
研究的目的:
- 通过广泛的计算机模拟,研究HCA异酶II和IX的pH取决的结构和动态特性.
- 阐明pH值变化对活性场所环境和质子穿机制的影响.
- 探索pH,酶构成和催化活性之间的关系.
主要方法:
- 对HCA异酶II和IX进行了广泛的分子动力学 (MD) 模拟.
- 分析的重点是结构稳定性,活性部位水合,局部静电潜力和各种pH值的水分子动力学.
- 使用自由能量计算和动力分析研究了His-64残留物的质子化状态和形状波动.
主要成果:
- HCA异酶II和IX的催化域的平衡结构和水合在很大程度上不受pH变化的影响.
- 在活性部位壁的局部静电潜力中观察到显著的pH依赖的变化.
- 活点水分子的动态和His-64残留物的质子化/定向状态显示出显著的pH敏感性,过渡速率在10^6和10^9s^-1.0之间.
结论:
- 虽然整体结构保持稳定,但pH值显著影响活性部位微环境和HCA异酶II和IX中的动态.
- 他的-64质子飞船的形状和质子状态动态是pH-依赖,影响其催化作用.
- 这些发现表明HCA活性由pH调节的机制,影响CO2水或HCO3脱水率.
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