Alber T, Gilbert W A, Ponzi D R, Petsko G A
Ciba Found Symp. 1983;93:4-24. doi: 10.1002/9780470720752.ch2.
Recent theoretical and experimental studies have demonstrated that proteins are fluctuating systems capable of large, seemingly random, excursions from the equilibrium conformation. Attention is now focusing on the functional consequences of these motions. X-ray diffraction is a powerful tool for mapping the spatial distribution of protein dynamics; studies on the temperature dependence of the apparent Debye-Waller factors of crystalline myoglobin demonstrate that proteins are flexible in the solid state. Crystallographic studies of a Michaelis complex of ribonuclease A show that a mobile lysine adapts its conformation to the changes in stereochemistry and charge distribution in the substrate during catalysis. The structure of the triose phosphate isomerase-substrate complex shows that a mobile region of 10 amino acids becomes ordered when ligand binds. These studies suggest several roles for protein mobility in enzymic catalysis: providing access to internal sites, allowing changes in substrate structure during the reaction, and reducing the observed binding constant of substrate and product to the enzyme by decreasing entropy. A flexible enzyme also does not need a communication system to signal binding or transformation, since a pre-existing equilibrium can be used. More speculative ideas, such as the guiding of thermal vibrations along the reaction coordinate, can only be tested when more detailed data are available.
最近的理论和实验研究表明，蛋白质是波动系统，能够从平衡构象进行大幅度的、看似随机的偏移。现在人们的注意力集中在这些运动的功能后果上。X射线衍射是绘制蛋白质动力学空间分布的有力工具；对结晶肌红蛋白的表观德拜-瓦勒因子的温度依赖性研究表明，蛋白质在固态下是灵活的。核糖核酸酶A的米氏复合物的晶体学研究表明，一个可移动的赖氨酸在催化过程中使其构象适应底物中立体化学和电荷分布的变化。磷酸丙糖异构酶-底物复合物的结构表明，当配体结合时，一个由10个氨基酸组成的可移动区域会变得有序。这些研究表明蛋白质流动性在酶催化中具有多种作用：提供进入内部位点的通道，允许反应过程中底物结构的变化，以及通过降低熵来降低底物和产物与酶的观测结合常数。一个灵活的酶也不需要一个通信系统来信号传递结合或转化，因为可以利用预先存在的平衡。更多推测性的想法，如沿着反应坐标引导热振动，只有在有更详细的数据时才能进行测试。
