(A) Allosteric Site 7 is located between TM3 (red)-TM5 (green)-TM6 (orange)-TM7 (cyan) in the intracellular mouth. In the X-ray structure, Site 7 clashes with TM6 that maintains strong interactions with TM3, precluding the binding of probe molecules. (B) In the active conformer, the bound probe molecules (ball-and-sticks) mainly interact with Arg1213.50, Val1253.54, Tyr2065.58, Ile2095.61, Thr3866.34 and Tyr4407.53 as highlighted in purple.