Selective binding of ligands to beta 1, beta 2 or chimeric beta 1/beta 2-adrenergic receptors involves multiple subsites.

摘要: The molecular basis of ligand binding selectivity to beta-adrenergic receptor subtypes was investigated by designing chimeric beta 1/beta 2-adrenergic receptors. These molecules consisted a set reciprocal constructions, obtained the exchange between wild-type genes one three unmodified transmembrane regions, together with their extracellular flanking regions. Eight different chimeras were expressed in Escherichia coli and studied selective ligands. evaluation relative effect each on affinity based analysis delta G values, calculated from equilibrium constants, as function number substituted domains. data showed that contribution exchanged region subtype varies ligand; moreover, while several regions are critical for pharmacological all ligands, others involved only some compounds. displayed compounds towards 1 or 2 thus results particular combination interactions subsites, variably distributed over seven receptor; these subsites presumably defined individual structural properties