Abstract
We deduced the three dimensional structures of transmembrane regions in human β 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 difrent between two models. Typical β adrenergic antagonist, propranolol, and long-lasting β antagonist, bopindolol, were docked in these models. The receptor-antagonist interactions were difrent 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 β1 and β2 subtypes, but low affinity to β3 subtype. The simulated receptor-antagonist relationships could account, in part, for the selectivity of the antagonists to the β subtypes.
