Audet Martin, Bouvier Michel
Department of Biochemistry, Institute for Research in Immunology and Cancer, Groupe de Recherche Universitaire sur le Médicament, Université de Montréal, CP 6128 Succursale Centre-Ville, Montréal, Québec H3C 3J7, Canada.
Nat Chem Biol. 2008 Jul;4(7):397-403. doi: 10.1038/nchembio.97.
With more than 800 members, the G protein-coupled receptor family constitutes the largest group of membrane proteins involved in signal transduction. Until the end of last year, high-resolution three-dimensional structures were available for only one of them--the light receptor rhodopsin. Recently the structure of the beta(2)-adrenergic receptor has been obtained, and it revealed interesting differences with the structure of rhodopsin. Analyses of these differences raise important questions about the binding modes of diffusible ligands in the receptor and allow formulation of testable hypotheses about the structural determinants linking drug binding to specific signaling responses. The three-dimensional structure derived from the beta(2)-adrenergic receptor crystal has been used to virtually dock ligands with distinct activities. The different binding modes of these ligands, which correlated with their reported efficacy profiles, suggest that it could be possible to predict the structural determinants of drug signaling efficacies.
G蛋白偶联受体家族拥有800多个成员，是参与信号转导的最大膜蛋白家族。截至去年年底，只有其中一种——光受体视紫红质——有高分辨率三维结构。最近，β-2肾上腺素能受体的结构已被解析，结果显示它与视紫红质的结构存在有趣的差异。对这些差异的分析提出了有关受体中可扩散配体结合模式的重要问题，并有助于形成关于将药物结合与特定信号反应联系起来的结构决定因素的可验证假设。源自β-2肾上腺素能受体晶体的三维结构已被用于虚拟对接具有不同活性的配体。这些配体的不同结合模式与其报道的效能概况相关，这表明有可能预测药物信号效能的结构决定因素。
