Orthosteric/Allosteric Bitopic Ligands

Molecular model of McN-A-343 docked in a bitopic mode to the M₂muscarinic receptor. Residues in green indicate orthosteric site amino acids that do not affect the binding of McN-A-343. The purple residue is a key orthosteric aspartic acid (D¹⁰³) in TM3 that acts as a counter ion for the ammonium headgroup. The blue tyrosine residue (Y¹⁷⁷), in the allosteric pocket, affects efficacy of McN-A-343. See text for details.