Rajarathnam Krishna, Rösgen Jörg
Department of Biochemistry and Molecular Biology, The University of Texas Medical Branch, Galveston, TX 77555, USA; Sealy Center for Structural Biology and Molecular Biophysics, The University of Texas Medical Branch, Galveston, TX 77555, USA.
Biochim Biophys Acta. 2014 Jan;1838(1 Pt A):69-77. doi: 10.1016/j.bbamem.2013.05.023. Epub 2013 Jun 5.
Integral membrane proteins, including G protein-coupled receptors (GPCR) and ion channels, mediate diverse biological functions that are crucial to all aspects of life. The knowledge of the molecular mechanisms, and in particular, the thermodynamic basis of the binding interactions of the extracellular ligands and intracellular effector proteins is essential to understand the workings of these remarkable nanomachines. In this review, we describe how isothermal titration calorimetry (ITC) can be effectively used to gain valuable insights into the thermodynamic signatures (enthalpy, entropy, affinity, and stoichiometry), which would be most useful for drug discovery studies, considering that more than 30% of the current drugs target membrane proteins. This article is part of a Special Issue entitled: Structural and biophysical characterisation of membrane protein-ligand binding.
整合膜蛋白，包括G蛋白偶联受体（GPCR）和离子通道，介导对生命各个方面都至关重要的多种生物学功能。了解分子机制，尤其是细胞外配体与细胞内效应蛋白结合相互作用的热力学基础，对于理解这些非凡的纳米机器的运作至关重要。在这篇综述中，我们描述了等温滴定量热法（ITC）如何能够有效地用于深入了解热力学特征（焓、熵、亲和力和化学计量），鉴于目前超过30%的药物靶向膜蛋白，这些特征对于药物发现研究将非常有用。本文是名为：膜蛋白-配体结合的结构和生物物理表征的特刊的一部分。
