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在E的α/β接口上的合规运动和水网. 大肠杆菌核酸减少酶
Clorice R Reinhardt1, Pengfei Li2, Gyunghoon Kang3,4
1Department of Molecular Biophysics and Biochemistry, Yale University, New Haven Connecticut 06520, United States.
Journal of the American Chemical Society
|July 8, 2020
概括
核酸减少酶 (RNR) 对于DNA合成至关重要. 分子动力学模拟揭示了Y356和Y731残留物如何通过E. coliRNR接口的质子合电子转移 (PCET) 促进基因转移,涉及接口水分子.
科学领域:
- 生物化学
- 结构生物学
- 计算生物学
背景情况:
- 核酸减少酶 (RNR) 是DNA合成的必需酶,催化核酸转化为脱氧核酸.
- 活性大肠杆菌Ia RNR是一种α2β2复合体,其催化过程涉及通过α/β接口通过质子合电子转移 (PCET) 的基因转移.
- 由于结构数据有限,在RNR接口的PCET的精确机制,特别是特定残留物和水分子的作用,仍然不太清楚.
研究的目的:
- 阐明在大肠杆菌RNRα/β接口沿着PCET通路的基因转移的原子层次机制.
- 研究界面残留物 (Y356和Y731) 和界面水的结构动态,结相互作用和形状灵活性.
- 提供有关界面水在促进PCET中的作用的见解.
主要方法:
- 在活性大肠杆菌Ia RNRα2β2复合物的高分辨率冷电子显微镜结构上进行了分子动力学 (MD) 模拟.
- 使用自由能量模拟来分析关键氨酸残留物 (Y731) 和它们的相互作用.
- 分析的重点是介面水结构,结网络以及在拟议的PCET路径上的残留动态.
主要成果:
- 模拟显示Y731可以采用不同的形状 (翻转出来和堆叠),以促进与Y356和Y730的PCET.
- Y356和Y731都与表面水分子进行结相互作用,其中一些形状显示出共享的桥梁水分子.
- 表面的水分子和与结合的水链似乎作为主要的质子受体,在Y356和Y731之间调解PCET.
结论:
- Y731的形状灵活性和涉及Y356,Y731和界面水的结相互作用对于有效的基因转移至关重要.
- 介面水在大肠杆菌RNR的质子合电子转移机制中起着至关重要的作用.
- 这些发现提供了与实验数据一致的原子级机理见解,进步了我们对RNR功能的理解.
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