Journal article

Role of Tyr356(7.43) and Ser190(4.57) in antagonist binding in the rat β1-adrenergic receptor

LA Rezmann-Vitti, TL Nero, GP Jackman, CA Machida, BJ Duke, WJ Louis, SNS Louis

Journal of Medicinal Chemistry | Published : 2006

Abstract

Site-directed mutagenesis and photoaffinity labeling experiments suggest the existence of at least two distinct binding orientations for aryloxypropanolamine competitive antagonists in the β-adrenergic receptor (β-AR), one where the aryloxy moiety is located near transmembrane α-helix 7 (tm 7) and another where it is near tm 5. To explore a hydrophobic pocket involving tms 1, 2, 3, and 7 for potential aryloxy interaction sites, we selected Tyr356(7.43) and Trp 134(3.28) in the rat β1-AR for site-directed mutagenesis studies. Ser190(4.57) was also investigated, as the equivalent residues are known antagonist interaction sites in the muscarinic M1 and the dopamine D2 receptors. Binding affinit..

View full abstract

Grants

Citation metrics