title: Molecular modeling of SWR-0342SA, a beta3-selective agonist, with beta1- and beta3-adrenoceptor.
abstract: The molecular dynamics (MD) simulations study in the formation of the complex between compound SWR-0342SA and beta-ARs suggested that upon binding SWR-0342SA stimulates receptor activation through residues network (Asp104, Leu335 in beta(1)-AR; Asp117, Ser209, Leu303, Ser191 in beta(3)-AR) in an active conformation state. The models suggest that the structural origin of the selectivity of SWR-0342SA to beta(3)-AR vs. beta(1)-AR comes from the following results: (a) the tight interaction between the agonist and the TMs 3, 5, 6 and 2 nd EC loop. Asp117 interacts with the cationic amino group of the agonist molecule. (b) Additional contacts are done with Ser209, Leu303 and Ser191. These results are in good agreement with the binding affinities (pKi values) of SWR-0342SA to beta-AR family expressed in recombinant mammalian cells.
authors.affiliation: Department of Pharmacology, Niigata University of Pharmacy and Applied Life Sciences, Niigata 950-2081, Japan.
authors.forename: Maruf
authors.initials: M
authors.lastname: Ahmed
authors.forename: Masaji
authors.initials: M
authors.lastname: Ishiguro
authors.forename: Takafumi
authors.initials: T
authors.lastname: Nagatomo
mesh_terms: D000085:Acetates / Q000737:chemistry* / Q000378:metabolism; D058665:Adrenergic beta-1 Receptor Agonists; D058667:Adrenergic beta-3 Receptor Agonists; D000318:Adrenergic beta-Agonists / Q000737:chemistry* / Q000378:metabolism; D000818:Animals; D001665:Binding Sites; D019556:COS Cells; D002522:Chlorocebus aethiops; D008958:Models, Molecular; D015394:Molecular Structure; D017434:Protein Structure, Tertiary; D018342:Receptors, Adrenergic, beta-1 / Q000378:metabolism; D022702:Receptors, Adrenergic, beta-3 / Q000378:metabolism
chemical_list: D000085:Acetates; D058665:Adrenergic beta-1 Receptor Agonists; D058667:Adrenergic beta-3 Receptor Agonists; D000318:Adrenergic beta-Agonists; D018342:Receptors, Adrenergic, beta-1; D022702:Receptors, Adrenergic, beta-3; C401286:SWR 0342SA