选择性波器对流感A M2通道中的质子选择性的影响
Todor Dudev1,2, Cédric Grauffel2, Carmay Lim2,3
1Faculty of Chemistry and Pharmacy, Sofia University , Sofia 1164, Bulgaria.
Journal of the American Chemical Society
|September 13, 2016
概括
流感A M2通道的质子选择性取决于histidine质子和过电荷. 一个带有两个质子的二离子过器增强了对等竞争性离子的选择性.
科学领域:
- 生物物理
- 结构生物学
- 计算化学
背景情况:
- 由于其在病毒复制中的作用,流感A M2质子通道是关键的治疗点.
- 该通道的选择性过器,由四个histidines线,对于区分质子和其他离子至关重要.
- 在His4过器中质子选择性的物理基础仍然不清楚.
研究的目的:
- 在M2通道的His4选择性过器中阐明控制质子选择性的物理原理.
- 调查胺质子化状态,溶剂暴露,寡合体状态和配体组成如何影响质子选择性.
- 确定质子选择性是否需要特定的胺质子化状态,以及替代残留物是否可以调节选择性.
主要方法:
- 在模型选择性过器中计算自由能量 (Na+与H3O+) 的评估.
- 分析包括胺质子化状态,溶剂暴露,寡合体状态和配体组成的因素.
- 模拟四度和三度过器,具有不同的西丁质子和连接体类型.
主要成果:
- 四聚基His4过器比三聚基His3过器具有更大的质子选择性.
- 与其他电荷状态相比,二化His4波器 (两个质子化histidines) 显示了增强的质子选择性.
- 通过在二氧化过器中为Na+等离子体创造低于最佳的结合来实现质子选择性.
结论:
- M2通道的质子选择性由胺质子化,过电荷和寡合状态调节.
- 双离子[His4]2+波器模型通过排斥竞争性离子来解释增强的质子选择性.
- 了解这些原则可以为设计针对质子运输的新型抗病毒疗法提供信息.
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