Proposed binding mode for salvinorin A.
A, putative interaction of salvinorin A with, among other residues, Ile316(7.39) and Ile290(6.51) in the KOR orthosteric binding site. Like U-69593, the close association of the ligand with TM7 probably interferes with the ability of TM7 to adopt a G protein-recognizing conformation. B, putative binding mode showing KOR amino acid residues within 4 Å of the ligand. Water molecules W1–W4 correspond to Wat1311, -1307, -1316, and -1314, respectively.