Resolving Binding Events on the Multifunctional Human Serum Albumin.,ChemMedChem

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Resolving Binding Events on the Multifunctional Human Serum Albumin.
ChemMedChem ( IF 3.6 ) Pub Date : 2020-03-19 , DOI: 10.1002/cmdc.202000069
Lea Wenskowsky ₁ , Michael Wagner ₂ , Johannes Reusch ₃ , Herman Schreuder ₂ , Hans Matter ₂ , Till Opatz ₁ , Stefan Matthias Petry ₂

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Physiological processes rely on initial recognition events between cellular components and other molecules or modalities. Biomolecules can have multiple sites or mode of interaction with other molecular entities, so that a resolution of the individual binding events in terms of spatial localization as well as association and dissociation kinetics is required for a meaningful description. Here we describe a trichromatic fluorescent binding- and displacement assay for simultaneous monitoring of three individual binding sites in the important transporter and binding protein human serum albumin. Independent investigations of binding events by X-ray crystallography and time-resolved dynamics measurements (switchSENSE technology) confirm the validity of the assay, the localization of binding sites and furthermore reveal conformational changes associated with ligand binding. The described assay system allows for the detailed characterization of albumin-binding drugs and is therefore well-suited for prediction of drug-drug and drug-food interactions. Moreover, conformational changes, usually associated with binding events, can also be analyzed.

中文翻译：

解决多功能人血清白蛋白的结合事件。

生理过程依赖于细胞成分和其他分子或模式之间的初始识别事件。生物分子可以具有与其他分子实体相互作用的多个位点或模式，因此需要在空间定位以及缔合和解离动力学方面解决各个结合事件才能进行有意义的描述。在这里，我们描述了一种三色荧光结合和置换测定，用于同时监测重要转运蛋白和结合蛋白人血清白蛋白中的三个单独的结合位点。通过 X 射线晶体学和时间分辨动力学测量（switchSENSE 技术）对结合事件进行独立研究，证实了测定的有效性、结合位点的定位，并进一步揭示了与配体结合相关的构象变化。所描述的测定系统可以详细表征白蛋白结合药物，因此非常适合预测药物-药物和药物-食物相互作用。此外，还可以分析通常与结合事件相关的构象变化。

更新日期：2020-03-19

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