Evolutionary optimization of the catalytic efficiency of enzymes.
Evolutionary optimization of the catalytic efficiency of enzymes.
复制标题
酶催化效率的进化优化。
DOI：
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发表时间：
1992
期刊：
影响因子：
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通讯作者：
Gösta Pettersson
中科院分区：
文献类型：
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作者：
Gösta Pettersson
1.速率方程的广义Michaelian类型的酶促反应机制进行了分析，以建立该机制应如何进行动力学设计，以优化酶的催化效率为一个给定的平均幅度的真实和表观的一级速率常数在该机制中，在给定浓度的酶，底物和产品。2.只要底物和产物结合到酶的速度常数没有达到扩散控制的缔合过程的极限值，酶操作的最佳状态的特征将是正向（真实和表观）一阶速率常数的大小相等，反向速率常数的大小相等。驱动催化反应的自由能的下降对于该机制中的每个反应步骤将以相等的程度发生。所有内部平衡常数将具有相等的量值，并且仅反映催化反应与平衡条件的接近程度。3.当底物和产物结合的速度常数的大小达到上限时，反应机制的最优动力学设计变得更加复杂，必须通过数值方法来建立。磷酸丙糖异构酶计算的数值解表明，这种特定的酶可能会或可能不会被认为是表现出接近最大效率，这取决于什么值被分配给配体缔合速率常数的上限。4.参数表明，没有有用的信息，可以通过以前采取的方法，是基于应用的线性自由能关系的速率和平衡常数的反应机制的进化优化酶的催化效率。
1. The rate equation for a generalized Michaelian type of enzymic reaction mechanism has been analyzed in order to establish how the mechanism should be kinetically designed in order to optimize the catalytic efficiency of the enzyme for a given average magnitude of true and apparent first-order rate constants in the mechanism at given concentrations of enzyme, substrate and product. 2. As long as on-velocity constants for substrate and product binding to the enzyme have not reached the limiting value for a diffusion-controlled association process, the optimal state of enzyme operation will be characterized by forward (true and apparent) first-order rate constants of equal magnitude and reverse rate constants of equal magnitude. The drop in free energy driving the catalysed reaction will occur to an equal extent for each reaction step in the mechanism. All internal equilibrium constants will be of equal magnitude and reflect only the closeness of the catalysed reaction to equilibrium conditions. 3. When magnitudes of on-velocity constants for substrate and product binding have reached their upper limits, the optimal kinetic design of the reaction mechanism becomes more complex and has to be established by numerical methods. Numerical solutions, calculated for triosephosphate isomerase, indicate that this particular enzyme may or may not be considered to exhibit close to maximal efficiency, depending on what value is assigned to the upper limit for a ligand association rate constant. 4. Arguments are presented to show that no useful information on the evolutionary optimization of the catalytic efficiency of enzymes can be obtained by previously taken approaches that are based on the application of linear free-energy relationships for rate and equilibrium constants in the reaction mechanism.