RT Journal Article SR Electronic T1 Glycine Hinges with Opposing Actions at the Acetylcholine Receptor-Channel Transmitter Binding Site JF Molecular Pharmacology JO Mol Pharmacol FD American Society for Pharmacology and Experimental Therapeutics SP 351 OP 359 DO 10.1124/mol.110.068767 VO 79 IS 3 A1 Purohit, Prasad A1 Auerbach, Anthony YR 2011 UL http://molpharm.aspetjournals.org/content/79/3/351.abstract AB The extent to which agonists activate synaptic receptor-channels depends on both the intrinsic tendency of the unliganded receptor to open and the amount of agonist binding energy realized in the channel-opening process. We examined mutations of the nicotinic acetylcholine receptor transmitter binding site (α subunit loop B) with regard to both of these parameters. αGly147 is an “activation” hinge where backbone flexibility maintains high values for intrinsic gating, the affinity of the resting conformation for agonists and net ligand binding energy. αGly153 is a “deactivation” hinge that maintains low values for these parameters. αTrp149 (between these two glycines) serves mainly to provide ligand binding energy for gating. We propose that a concerted motion of the two glycine hinges (plus other structural elements at the binding site) positions αTrp149 so that it provides physiologically optimal binding and gating function at the nerve-muscle synapse.