Accuracy of Substrate Selection by Enzymes Is Controlled by Kinetic Discrimination
Accuracy of Substrate Selection by Enzymes Is Controlled by Kinetic Discrimination
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DOI：
10.1021/acs.jpclett.7b00441
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发表时间：
2017-04-06
影响因子：
5.7
通讯作者：
Igoshin, Oleg A.
中科院分区：
文献类型：
--
作者：
Banerjee, Kinshuk;Kolomeisky, Anatoly B.;Igoshin, Oleg A.
酶具有从化学相似的分子库中选择正确底物的非凡能力。这种选择的准确性取决于正确和错误反应途径的自由能分布的差异。在这里，我们调查的自由能景观的功能管理的变化和最小化的选择性误差。一般认为，最小误差受动力学（活化势垒高度）和热力学（结合稳定性）因素的影响。与此相反，使用第一次通过理论分析，我们表明，稳态选择性误差仅由途径之间的过渡态能量的差异，是独立的稳定复合物的能量。结果说明了两种常见的催化机制：（i）的Michaelis-Menten计划和（ii）的纠错动力学校对计划与tRNA选择和DNA复制作为指导生物学的例子。因此，我们的理论分析表明，选择性机制总是动力学控制。
Enzymes have the remarkable ability to select the correct substrate from the pool of chemically similar molecules. The accuracy of such a selection is determined by differences in the free-energy profiles for the right and wrong reaction pathways. Here, we investigate which features of the free-energy landscape govern the variation and minimization of selectivity error. It is generally believed that minimal error is affected by both kinetic (activation barrier heights) and thermodynamic (binding stability) factors. In contrast, using first-passage theoretical analysis, we show that the steady-state selectivity error is determined only by the differences in transition-state energies between the pathways and is independent of the energies of the stable complexes. The results are illustrated for two common catalytic mechanisms: (i) the Michaelis-Menten scheme and (ii) an error-correcting kinetic proofreading scheme with tRNA selection and DNA replication as guiding biological examples. Our theoretical analysis therefore suggests that the selectivity mechanisms are always kinetically controlled.