Distinguishing induced fit from conformational selection
Distinguishing induced fit from conformational selection
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DOI：
10.1016/j.bpc.2014.03.003
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发表时间：
2014-05-01
影响因子：
3.8
通讯作者：
Jemth, Per
中科院分区：
文献类型：
--
作者：
Gianni, Stefano;Dogan, Jakob;Jemth, Per
蛋白质和配体之间的相互作用通常涉及蛋白质的构象变化。这种构象变化可以发生在与配体结合之前(构象选择)或之后(诱导配位)。当观察到双曲线结合动力学时，通常很难区分诱导匹配和构象选择。根据本杂志最近发表的一篇论文(Vogt等人，生物物理学。186,2014，13-21)以及目前对结合机制的兴趣，这些结合机制来自对蛋白质结构域中不同构象的观察样本，以及来自内在无序蛋白质领域的兴趣，我们在这里描述了一种动力学方法，至少在某些情况下，它明确地将诱导适配与构象选择区分开来。该方法依赖于在单独的实验中测量观察到的结合和改变蛋白质和配体的速率常数A。虽然诱导配对总是产生与A.值增加的双曲线依赖关系，但当配体和蛋白质(显示构象变化)浓度在不同的实验中变化时，构象选择机制产生不同的动力学。我们提供了文献中的例子，并讨论了该方法的局限性。(C)2014爱思唯尔B.V.保留所有权利。
The interactions between proteins and ligands often involve a conformational change in the protein. This conformational change can occur before (conformational selection) or after (induced fit) the association with ligand. It is often very difficult to distinguish induced fit from conformational selection when hyperbolic binding kinetics are observed. In light of a recent paper in this journal (Vogt et al., Biophys. Chem., 186, 2014, 13-21) and the current interest in binding mechanisms emerging from observed sampling of distinct conformations in protein domains, as well as from the field of intrinsically disordered proteins, we here describe a kinetic method that, at least in some cases, unequivocally distinguishes induced fit from conformational selection. The method relies on measuring the observed rate constant A. for binding and varying both the protein and the ligand in separate experiments. Whereas induced fit always yields a hyperbolic dependence of increasing A. values, the conformational selection mechanism gives rise to distinct kinetics when the ligand and protein (displaying the conformational change) concentration is varied in separate experiments. We provide examples from the literature and discuss the limitations of the approach. (C) 2014 Elsevier B.V. All rights reserved.