标题:
β2肾上腺素受体结构研究进展Current Progress of Structural Studies on β2 Adrenergic Receptor
作者:
唐令利, 张鹏, 王先龙
关键字:
β2肾上腺素受体, G蛋白偶联受体, 晶体结构, 激动剂, 反向激动剂, 拮抗剂β2 Adrenergic Receptor, G Protein-Coupled Receptor, Crystal Structure, Agonist, Inverse Agonist, Antagonist
期刊名称:
《Hans Journal of Medicinal Chemistry》, Vol.3 No.1, 2015-03-24
摘要:
β2肾上腺素受体(β2 adrenergic receptor, β2AR)是生命体中一类重要的G蛋白偶联受体。作为一种膜蛋白，由于结晶困难过去很难获得其晶体三维结构。近几年来，得益于蛋白质结晶技术和自由电子X射线晶体结构测定技术的进展，各种状态下的β2AR晶体结构获得解析。β2AR结构的发现丰富了人们对生命现象的解释，对于当今新药物设计具有重大意义。本文主要综述了β2肾上腺素受体晶体结构的发现历程、结构特征与不同类型配体(激动剂、反向激动剂和拮抗剂)的相互作用机制以及其在临床医学上的应用研究，并指出这一研究领域的未来发展方向。Beta-2 adrenergic receptor is an important member among G protein-coupled receptors superfa-mily. As a membrane protein, it is difficult to crystalize and its three-dimensional structure is not known until recent years. Thanks to the development of the crystal engineering techniques and the breakthroughs in the free electron X-ray laser crystallography, many crystal structures of β2 adrenergic receptor at different states become available now. The discovery of the crystal structure β2 adrenergic receptor has enriched our understanding on many life phenomena and its impact to the structure-based drug design cannot be overestimated. We review the discovery history of β2 adrenergic receptor crystal structures, the structural characteristics of the receptor, the in-teractions between the receptor and different subtypes of the ligands (agonist, inverse agonist and antagonist) and clinical applications.