Conformational selection is a dominant mechanism of ligand binding.
Conformational selection is a dominant mechanism of ligand binding.
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DOI：
10.1021/bi400929b
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发表时间：
2013-08-27
期刊：
影响因子：
2.9
通讯作者：
Di Cera, Enrico
中科院分区：
文献类型：
--
作者：
Vogt, Austin D.;Di Cera, Enrico
生物大分子中的分子识别是通过与结合步骤之前或之后的构象转变耦合的结合相互作用实现的，两种限制机制分别称为构象选择和诱导匹配。整理这些机制对任何结合作用的贡献仍然是生物化学中普遍感兴趣的一项具有挑战性的任务。在这里，我们表明构象选择与大量的动力学行为有关，作为配体结合的一种机制，构象选择永远不能被先验地证明是错误的，并且足以解释大量体系的实验记录的松弛动力学。另一方面，诱导匹配的特点是动力学行为的频谱很窄，在构象选择提供唯一可能解释的许多情况下可能会被证明是错误的。这一结论提供了松弛动力学分析的范式转变，构象选择作为配体结合的一种机制获得了优势。构象选择的主导作用支持了大分子作为构象系综的新兴结构观点，配体从构象系综中选择初始的最佳匹配来产生生物响应。
Molecular recognition in biological macromolecules is achieved by binding interactions coupled to conformational transitions that precede or follow the binding step, two limiting mechanisms known as conformational selection and induced fit, respectively. Sorting out the contribution of these mechanisms to any binding interaction remains a challenging task of general interest in biochemistry. Here we show that conformational selection is associated with a vast repertoire of kinetic behaviors, can never be disproved a priori as a mechanism of ligand binding, and is sufficient to explain the relaxation kinetics documented experimentally for a large number of systems. On the other hand, induced fit features a narrow spectrum of kinetic behaviors and can be disproved in many cases where conformational selection offers the only possible explanation. This conclusion offers a paradigm shift in the analysis of relaxation kinetics, with conformational selection acquiring pre-eminence as a mechanism of ligand binding. The dominant role of conformational selection supports the emerging structural view of the macromolecule as a conformational ensemble from which the ligand selects the initial optimal fit to produce a biological response.
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