Qiu Weihong, Zhang Luyuan, Okobiah Oghaghare, Yang Yi, Wang Lijuan, Zhong Dongping, Zewail Ahmed H
Department of Physics, 191 West Woodruff Avenue, The Ohio State University, Columbus, Ohio 43210, USA.
J Phys Chem B. 2006 Jun 1;110(21):10540-9. doi: 10.1021/jp055989w.
Human serum albumin, the most abundant protein found in blood plasma, transports a great variety of ligands in the circulatory system and undergoes reversible conformational transitions over a wide range of pH values. We report here our systematic studies of solvation dynamics and local rigidity in these conformations using a single intrinsic tryptophan (W214) residue as a local molecular probe. With femtosecond resolution, we observed a robust bimodal distribution of time scales for all conformational isomers. The initial solvation occurs in several picoseconds, representing the local librational/rotational motions, followed by the dynamics, in the tens to hundreds of picoseconds, which result from the more bonded water in the tryptophan crevice. Under the physiological condition of neutral pH, we measured approximately 100 ps for the decay of the solvation correlation function and observed a large wobbling motion at the binding site that is deeply buried in a crevice, revealing the softness of the binding pocket and the large plasticity of the native structure. At acidic pH, the albumin molecule transforms to an extended conformation with a large charge distribution at the surface, and a similar temporal behavior was observed. However, at the basic pH, the protein opens the crevice and tightens its globular structure, and we observed significantly faster dynamics, 25-45 ps. These changes in the solvation dynamics are correlated with the conformational transitions and related to their structural integrity.
人血清白蛋白是血浆中含量最丰富的蛋白质，在循环系统中运输多种配体，并在很宽的pH值范围内发生可逆的构象转变。我们在此报告了我们使用单个内在色氨酸（W214）残基作为局部分子探针，对这些构象中的溶剂化动力学和局部刚性进行的系统研究。以飞秒分辨率，我们观察到所有构象异构体的时间尺度存在稳健的双峰分布。初始溶剂化发生在几皮秒内，代表局部振动/旋转运动，随后是几十到几百皮秒内的动力学，这是由色氨酸缝隙中结合更紧密的水引起的。在中性pH的生理条件下，我们测量到溶剂化相关函数的衰减约为100皮秒，并观察到深埋在缝隙中的结合位点存在大幅摆动运动，揭示了结合口袋的柔软性和天然结构的大可塑性。在酸性pH下，白蛋白分子转变为表面具有大电荷分布的伸展构象，并观察到类似的时间行为。然而，在碱性pH下，蛋白质打开缝隙并收紧其球状结构，我们观察到动力学明显更快，为25 - 45皮秒。这些溶剂化动力学的变化与构象转变相关，并与其结构完整性有关。
