Fig. 4.

The orthosteric binding site and secondary binding pockets. (A) All the identified ligand-contacting positions for the aminergic receptors are mapped onto a β₂AR structure (PDB ID 4LDO). The 12 OBS residues are in cyan, and the SBP residues are in yellow. Three representative SBPs shown in (C–E) are indicated by red dotted circles. (B) A zoomed-in view of the OBS in the β₂AR bound with adrenaline (PDB ID 4LDO). The side chains of the three highly conserved residues within the aminergic family, Asp^3.32, Trp^6.48, and Tyr^7.43, and the conserved EL^2.50-Cys^3.25 disulfide bond are shown as sticks; for all other residues, sticks were drawn from the Cα to the center of mass (represented as spheres) of the heavy atoms of the side chain. The zoomed-in views of the SBPs, “SBP₂₃₇” (C), “SBP₅₆₇” (D), “SBP₃₄₅₆” (E), are shown in representative structures [PDB IDs 4AMI (C), 4IB4 (D), 3UON (E)]. The SBPs are classified according to their locations and named according to the surrounding TMs (see Fig. 2). The ligands in the respective structures are in spheres with the carbon atoms of adrenaline (B) or the moieties occupying the SBPs (C–E) colored in orange.