Demetrius L
Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, MA 02138, USA.
J Theor Biol. 1998 Sep 21;194(2):175-94. doi: 10.1006/jtbi.1998.0748.
Site-directed mutagenesis has proved an effective experimental technique to investigate catalytic mechanisms and to determine relations between enzyme structure and function. This article invokes an analytical model based on evolution by mutation and natural selection-Nature's analogue of site-directed mutagenesis-to derive a set of general rules relating enzyme structure and activity. The catalysts are described in terms of the structural parameters, rigidity and flexibility, and the functional variables, reaction rate and substrate specificity. The evolutionary model predicts the following structure-activity relations: (a) rigid enzyme-flexible substrate: large variation in reaction rates, broad substrate specificity; (b) rigid enzyme-rigid substrate: diffusion controlled rates, absolute specificity; (c) flexible enzyme-rigid substrate: intermediate reaction rates, group specificity; (d) flexible enzyme-flexible substrate: slow rates, absolute specificity. Spectroscopic methods and X-ray crystallography now yield important characteristics of enzyme-substrate complexes such as molecular flexibility. The evolutionary analysis we have exploited provides general principles for inferring catalytic activity from structural studies of enzyme-substrate complexes.
定点突变已被证明是一种有效的实验技术，可用于研究催化机制以及确定酶结构与功能之间的关系。本文引入了一种基于突变和自然选择进化的分析模型——自然界中定点突变的类似物——以推导一组关于酶结构与活性的通用规则。从结构参数、刚性和柔性以及功能变量、反应速率和底物特异性等方面对催化剂进行了描述。进化模型预测了以下结构-活性关系：（a）刚性酶-柔性底物：反应速率变化大，底物特异性宽泛；（b）刚性酶-刚性底物：扩散控制速率，绝对特异性；（c）柔性酶-刚性底物：中等反应速率，基团特异性；（d）柔性酶-柔性底物：速率缓慢，绝对特异性。光谱方法和X射线晶体学现在可以得出酶-底物复合物的重要特征，如分子柔性。我们所采用的进化分析为从酶-底物复合物的结构研究中推断催化活性提供了一般原则。
