title: Recent structural advances of β1 and β2 adrenoceptors yield keys for ligand recognition and drug design.
abstract: Because they represent attractive drug targets, adrenoceptors have been widely studied. Recent progress in structural data of β-adrenoceptors allows us to understand and predict key interactions in ligand recognition and receptor activation. Nevertheless, an important aspect of this process has only begun to be explored: the stabilization of a conformational state of these receptors upon contact with a ligand and the capacity of a ligand to influence receptor conformation through allosteric modulation, biased signaling, and selectivity. The aim of the present Perspective is to identify the well-defined orthosteric binding site and possible allosteric sites and to analyze the importance of the ligand-receptor interaction in the stabilization of certain receptor conformations. For this purpose, we have reviewed recent advances made through the use of X-ray data from ligand-β-adrenoceptor (including ADRB1 and ADRB2) crystal structures. Most importantly, implications in the medicinal chemistry field are explored in relation to drug design.
authors.affiliation: Departments of Biochemistry and Physiology, Laboratory of Molecular Modeling and Bioinformatics, Postgraduate Research Section, Escuela Superior de Medicina, Instituto Politécnico Nacional , Plan de San Luis y Dı́az Mirón s/n, Mexico City, 11340, Mexico.
authors.forename: Marvin A
authors.initials: MA
authors.lastname: Soriano-Ursúa
authors.forename: José G
authors.initials: JG
authors.lastname: Trujillo-Ferrara
authors.forename: José
authors.initials: J
authors.lastname: Correa-Basurto
authors.forename: Santiago
authors.initials: S
authors.lastname: Vilar
mesh_terms: D015195:Drug Design; D006801:Humans; D008024:Ligands; D008958:Models, Molecular; D008968:Molecular Conformation; D018342:Receptors, Adrenergic, beta-1 / Q000737:chemistry* / Q000378:metabolism; D018343:Receptors, Adrenergic, beta-2 / Q000737:chemistry* / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D008024:Ligands; D018342:Receptors, Adrenergic, beta-1; D018343:Receptors, Adrenergic, beta-2