[HTML][HTML] Molecular determinants of allosteric modulation at the M1 muscarinic acetylcholine receptor
Benzylquinolone carboxylic acid (BQCA) is an unprecedented example of a selective
positive allosteric modulator of acetylcholine at the M 1 muscarinic acetylcholine receptor
(mAChR). To probe the structural basis underlying its selectivity, we utilized site-directed
mutagenesis, analytical modeling, and molecular dynamics to delineate regions of the M 1
mAChR that govern modulator binding and transmission of cooperativity. We identified Tyr-
85 2.64 in transmembrane domain 2 (TMII), Tyr-179 and Phe-182 in the second extracellular …
positive allosteric modulator of acetylcholine at the M 1 muscarinic acetylcholine receptor
(mAChR). To probe the structural basis underlying its selectivity, we utilized site-directed
mutagenesis, analytical modeling, and molecular dynamics to delineate regions of the M 1
mAChR that govern modulator binding and transmission of cooperativity. We identified Tyr-
85 2.64 in transmembrane domain 2 (TMII), Tyr-179 and Phe-182 in the second extracellular …