Chakraborty Pradipta, Di Cera Enrico
Edward A. Doisy Department of Biochemistry and Molecular Biology, Saint Louis University School of Medicine , St. Louis, Missouri 63104, United States.
Biochemistry. 2017 Jun 6;56(22):2853-2859. doi: 10.1021/acs.biochem.7b00340. Epub 2017 May 22.
Conformational selection (CS) and induced fit (IF) are two widely used interpretations of binding of a ligand to biological macromolecules. Both mechanisms envision a two-step reaction in which a conformational transition either precedes (CS) or follows (IF) the binding step. Under pseudo-first-order conditions where the ligand is in excess compared to the macromolecule, both mechanisms produce two relaxations. A fast one eventually increases linearly with ligand concentration and reflects the binding interaction. A slow one saturates to a constant value after decreasing or increasing hyperbolically with ligand concentration. This relaxation is the one most often accessible to experimental measurements and is potentially diagnostic of the mechanism involved. A relaxation that decreases unequivocally identifies CS, but a hyperbolic increase is compatible with both CS and IF. The potential ambiguity between the two mechanisms is more than qualitative. Here we show that the entire kinetic repertoire of IF is nothing but a mathematical special case of CS as revealed by a simple transformation of the rate constants, which emphasizes the need for independent support of either mechanism from additional experimental evidence. We discuss a simple strategy for distinguishing between IF and CS under the most common conditions encountered in practice, i.e., when the ligand is in excess compared to the macromolecule and a single relaxation is accessible to experimental measurements.
构象选择（CS）和诱导契合（IF）是对配体与生物大分子结合的两种广泛使用的解释。两种机制都设想了一个两步反应，其中构象转变要么在结合步骤之前（CS），要么在结合步骤之后（IF）。在配体相对于大分子过量的伪一级条件下，两种机制都会产生两种弛豫。一种快速弛豫最终会随配体浓度线性增加，并反映结合相互作用。一种缓慢弛豫在随配体浓度呈双曲线下降或上升后会饱和到一个恒定值。这种弛豫是实验测量中最常能获取的，并且可能有助于判断所涉及的机制。明确下降的弛豫可确定为CS，但双曲线上升则与CS和IF都相符。两种机制之间的潜在模糊性不仅仅是定性的。在这里我们表明，IF的整个动力学特征只不过是CS的一种数学特例，这是通过速率常数的简单变换揭示的，这强调了需要从额外的实验证据中获得对任何一种机制的独立支持。我们讨论了一种在实际中最常见的条件下区分IF和CS的简单策略，即当配体相对于大分子过量且实验测量可获得单一弛豫时。
