分子动力学揭示了鱼类和哺乳动物脱氧血红蛋白在死后的pH值时独特的远距离西斯蒂丁位置和界面过渡
Sean Baker1, Mark P Richards1,2
1Department of Food Science, University of Wisconsin-Madison, Madison, Wisconsin 53706, United States.
Journal of agricultural and food chemistry
|August 8, 2025
概括
鱼血红蛋白 (Hb) 由于结构上的差异,具有比牛Hb更高的氧化能力. 这些包括一个更稳定的四聚体形成和一个HisE7的方向,这有利于氧化剂进入heme口袋.
科学领域:
- 生物化学 生物化学
- 结构生物学 结构生物学
- 计算化学的计算化学
背景情况:
- 血红蛋白 (Hb) 在不同物种中表现出不同的氧化能力,影响其生理作用.
- 鱼血红蛋白IV (鱼IV Hb) 以其增强的氧化能力而闻名,与哺乳动物血红蛋白相比,如牛Hb.
- 了解这些差异需要对结构和功能性质进行详细的分析.
研究的目的:
- 阐明与牛Hb相比,鱼IV Hb的增强氧化能力背后的分子机制.
- 为了研究氨基酸变异在血口袋和α1-β2接口中的作用.
- 评估远端胺 (HisE7) 质子化状态对Hb功能的影响.
主要方法:
- 分子动力学 (MD) 模拟来分析蛋白质动力学和相互作用.
- 对heme口袋和子单位间接口特征的计算分析.
- 使用尺寸排除色谱和酶活性测定进行实验验证.
主要成果:
- 与牛Hb (PheCE4) 相比,鱼IV Hb表现出更强的π-π堆叠相互作用 (TrpCE4),影响了HisE7的方向.
- 牛Hb中的HisE7可以在中性pH下采取"上升"的形状,但在低pH下会"下降",与鱼IV Hb不同.
- 鱼IV Hb显示出更大的倾向于四聚体形成和HisE7"上升"定位,创建一个氧化剂可访问的通道.
- 牛Hb在低pH下表现出较高的酸盐还原酶活性,与HisE7定向相关.
结论:
- 鱼IV Hb的增强的亲氧化能力归因于其增加的亚单元关联倾向和HisE7.7持续的"向上"方向.
- 鱼IV Hb的这些结构特征有助于氧化剂进入血口袋,使其与牛Hb区别开来.
- 介面差异在低pH值的鱼类中促进了四聚体解离,与哺乳动物的Hb行为形成鲜明对比.
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