在蛋白质中控制Zn结合的histidine质子化状态的因素:DFT/CDM研究
1Institute of Biomedical Science, Academic Sinica, Taipei 11529, Taiwan ROC.
Journal of the American Chemical Society
|February 26, 2004
概括
在结位的histidine的质子化状态取决于溶剂可达性和.
科学领域:
- 生物化学 生物化学
- 计算化学计算化学
- 结构生物学 结构生物学
背景情况:
- 伊斯蒂丁质子化状态对于酶功能至关重要.
- 结合站点通常具有His-Asp/Glu三合体.
- 了解这些部位是阐明酶机制的关键.
研究的目的:
- 调查影响His质子在Zn结合位点的因素.
- 确定第二联体在质子转移中的作用.
- 评估Zn-His-Asp/Glu三合物的对Zn结合水的影响.
主要方法:
- 量子力学和连续介电学计算的结合.
- 计算出了Zn结合的伊米达/水脱质的自由能量.
- 分析了各种Zn复合模型.
主要成果:
- 质子化状态由金属结合部位的溶剂可访问性和 Zn Lewis 酸度来决定.
- 第二层联体,包括骨干碳基,可以接受质子.
- 三合体中的Asp/Glu可以在埋藏的腔内稳定阴离子.
结论:
- 它的质子是对微环境敏感的.
- 第二层相互作用在调节金属位置特性方面发挥着重要作用.
- 这些发现与金属酶的实验观察结果一致.
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