Conserved binding mode of human beta2 adrenergic receptor inverse agonists and antagonist revealed by X-ray crystallography.

ABSTRACT: G protein-coupled receptors (GPCRs) represent a large fraction of current pharmaceutical targets, and of the GPCRs, the beta(2) adrenergic receptor (beta(2)AR) is one of the most extensively studied. Previously, the X-ray crystal structure of beta(2)AR has been determined in complex with two partial inverse agonists, but the global impact of additional ligands on the structure or local impacts on the binding site are not well-understood. To assess the extent of such ligand-induced conformational differences, we determined the crystal structures of a previously described engineered beta(2)AR construct in complex with two inverse agonists: ICI 118,551 (2.8 A), a recently described compound (2.8 A) (Kolb et al, 2009), and the antagonist alprenolol (3.1 A). The structures show the same overall

SUBMITTER: Wacker D 

PROVIDER: S-EPMC2923663 | biostudies-literature | 2010 Aug

REPOSITORIES: biostudies-literature