[Modeling study of three-dimensional structure of human beta adrenoceptors and receptor-antagonists interactions]

We deduced the three dimensional structures of transmembrane regions in human beta adrenoceptors by computer simulating using the 2D electron density maps of bacteriorhodopsin and frog rhodopsin as templates. The deduced membrane-spanning helical regions, their arrangements and axes to the membrane plain were different between two models. Typical beta adrenergic antagonist, propranolol, and long-lasting beta antagonist, bopindolol, were docked in these models. The receptor-antagonist interactions were different between both models, in which the 3, 4, 5 and 6th transmembrane domains might participate in the antagonists-binding in both models, however, the amino acid residues in the domains contributing to the binding might be different between models. Propranolol and bopindolol have high affinity to beta 1 and beta 2 subtypes, but low affinity to beta 3 subtype. The simulated receptor-antagonist relationships could account, in part, for the selectivity of the antagonists to the beta subtypes.