SOLVENT VISCOSITY AND PROTEIN DYNAMICS
SOLVENT VISCOSITY AND PROTEIN DYNAMICS
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DOI：
10.1021/bi00564a001
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发表时间：
1980-01-01
期刊：
影响因子：
2.9
通讯作者：
YUE, KT
中科院分区：
文献类型：
--
作者：
BEECE, D;EISENSTEIN, L;YUE, KT
蛋白质是动态系统。最近的证据表明，它们存在于大量的构象亚态，并可以连续地从一个亚态移动到另一个亚态;蛋白质内的小配体的运动可能只通过这些构象波动。为了验证这一想法，闪光光解被用来研究在许多不同的溶剂中，CO与血红素的结合以及O2和CO与[抹香鲸]肌红蛋白（Mb）的结合。对这些实验的标准评价仅产生关于蛋白质-溶剂系统的信息。提出了一种新的方法，它允许有关蛋白质的结论：从所有溶剂的数据被认为是在一起，并在各种障碍的配体的过渡率作为固定的溶剂粘度的温度的函数进行了研究。在很宽的粘度范围内，血红素-CO的转变速率与溶剂粘度成反比，因此可以用Kramers方程描述。O2和CO在Mb中的速率也取决于溶剂粘度，并且在最低粘度下对溶剂最敏感。粘度甚至在水溶液中也会影响蛋白质反应。这些数据可以被解释的动态模型，在该模型中，转换成和内部Mb的构象子状态对应于封闭和开放的途径之间的波动。因此，配体运动主要由栅极而不是由静态势垒控制。确定了子态的一些特征参数，它们与穆斯堡尔实验中发现的类似参数近似一致。正如预期的那样，在新的方法中评估的障碍参数明显偏离由传统的程序获得的。与模型计算或基本理论的比较只有在新的评价中才有意义，并且该方法可能对许多或可能所有的生化反应都是必不可少的。
Proteins are dynamic systems. Recent evidence demonstrates that they exist in a large number of conformational substates and can continuously move from one substate to another; motion of a small ligand inside a protein may be possible only through these conformational fluctuations. To test this idea, flash photolysis was used to study the binding of CO to protoheme and O2 and CO to [sperm whale] myoglobin (Mb) in many different solvents. The standard evaluation of such experiments yields information only about the protein-solvent system. A novel approach is presented which permits conclusions concerning the protein: Data from all solvents are considered together, and the rates for transitions of the ligand over various barriers are studied as a function of temperature for fixed solvent viscosities. Over a wide range in viscosity the transition rates in heme-CO are inversely proportional to the solvent viscosity and can consequently be described by the Kramers equation. The rates of O2 and CO in Mb also depend on the solvent viscosity and are most sensitive to the solvent at the lowest viscosity. Viscosity influences protein reactions even in aqueous solutions. The data can be interpreted by a dynamic model in which transitions into and inside Mb are governed by fluctuations between conformational substates corresponding to closed and open pathways. Ligand motion thus is mainly controlled by gates and not by static potential barriers. Some characteristic parameters for the substates are determined, and they agree approximately with similar parameters found in Moessbauer experiments. As expected, the barrier parameters evaluated in the novel approach deviate markedly from the ones obtained by the conventional procedure. Comparison with model calculations or basic theories will be meaningful only with the new evaluation, and the method may be essential for many or possibly all biochemical reactions.