涉及酸化氨基酸侧链的键的强度
Daniel J Mandell1, Ilya Chorny, Eli S Groban
1Graduate Program in Biological and Medical Informatics, Department of Pharmaceutical Chemistry, and Graduate Group in Biophysics, University of California, San Francisco, California 94143, USA.
Journal of the American Chemical Society
|January 25, 2007
概括
这项研究量化了酸化氨基酸 (pSer,pAsp) 和常见的供体之间的键强度. 氨酸与酸化残留物形成更强的盐桥,而不是氨酸.
科学领域:
- 生物化学 生物化学
- 结构生物学 结构生物学
- 计算化学计算化学
背景情况:
- 翻译后酸化对于调节蛋白质功能至关重要.
- 了解涉及酸化残留物的相互作用是破译信号通路的关键.
- 酸盐的质子化状态影响其化学性质和相互作用.
研究的目的:
- 量化评估涉及化 (pSer) 和酸盐 (pAsp) 侧链的键的相对强度.
- 为了比较 arginine (Arg) 和 lysine (Lys) 与化残留物的结能力.
- 为了研究酸盐质子化状态对键稳定性的影响.
主要方法:
- 利用多个计算化学水平:明确的溶剂分子动力学,隐性溶剂分子力学和具有自相一致的反应场的量子力学.
- 由于生理的pH值,被认为是质子化和不质子化酸盐状态.
- 分析了各种键几何形状,包括充电-充电相互作用.
主要成果:
- 与氨酸 (Lys) 相比,氨酸 (Arg) 与酸化侧链形成明显更强的盐桥.
- 素 (pSer) 作为一个比二酸 (pAsp) 更稳定的键受体.
- 酸盐的质子化状态对键强度有微妙但明显的影响,对pAsp比pSer更为如此.
结论:
- 氨酸是通过盐桥稳定酸化残留物的卓越合作伙伴.
- pSer和pAsp具有不同的键稳定性,而pSer更为有利.
- 计算方法为生物系统中酸化介导相互作用的细微差别提供了宝贵的见解.
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