Obfuscation of allosteric structure-function relationships by enthalpy-entropy compensation
Obfuscation of allosteric structure-function relationships by enthalpy-entropy compensation
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DOI：
10.1016/s0006-3495(98)77589-7
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发表时间：
1998-08-01
影响因子：
3.4
通讯作者：
Reinhart, GD
中科院分区：
文献类型：
--
作者：
Tlapak-Simmons, VL;Reinhart, GD
嗜热脂肪芽孢杆菌磷酸果糖激酶 (PFK) 变构特性的 pH 和温度依赖性已分别在 5 至 9 和 6 至 40 摄氏度下进行了研究。在此 pH 和温度范围内，变构配体 MgADP 和磷酸（烯醇）丙酮酸 (PEP) 对 k(cat) 没有影响。当 pH 升高时，底物、果糖 6-磷酸和变构配体的解离常数以及这些配体之间的偶联自由能的绝对值均增加，表明尽管每个配体的亲和力稍低，但 PEP 的抑制作用和 MgADP 的活化作用增加。然而，随着 pH 值的增加，成分耦合焓和熵的绝对值显着减小，这表明变构配体结合产生的分子扰动的大小与这些扰动的功能后果的大小不相关。温度和 pH 值通过改变很大程度上补偿 Delta H 和 T Delta S 项对耦合自由能的相对贡献来对观察到的变构行为产生影响。
The pH and temperature dependence of the allosteric properties of phosphofructokinase (PFK) from Bacillus stearothermophilus have been studied from 5 to 9 and 6 to 40 degrees C, respectively. Throughout this pH and temperature range the allosteric ligands MgADP and phospho(enol)pyruvate (PEP) have no effect on k(cat). The dissociation constants of the substrate, fructose 6-phosphate, and the allosteric ligands, as well as the absolute value of the coupling free energies between these ligands, all increase when the pH is raised, indicating that the inhibition by PEP and the activation by MgADP increase despite each ligand's somewhat lower affinity. However, the constituent coupling enthalpies and entropies substantially diminish in absolute value as pH is increased, suggesting that the magnitudes of molecular perturbations engendered by the binding of allosteric ligands do not correlate with the magnitudes of the functional consequences of those perturbations. Temperature and pH exert their influence on the observed allosteric behavior by changing the relative contributions made by the largely compensating Delta H and T Delta S terms to the coupling free energy.