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Roland Baur, Marie Kielar, Lars Richter, Margot Ernst, Gerhard F. Ecker and Erwin Sigel Molecular analysis of the site for 2-arachidonylglycerol (2-AG) on the β2 subunit of GABAA receptors Journal of Neurochemistry 126

Article first published online: 3 MAY 2013 | DOI: 10.1111/jnc.12270

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This study describes the binding site for 2-arachidonyl glycerol (2-AG) on β2 subunit-containing GABAA receptors. From the fact that the important amino acid residues in the fourth transmembrane segment (M4) span > 18 Å, we conclude that the hydrophobic tail of the bound 2-AG molecule must be near linear and that the site mainly locates to the inner leaflet of the bilayer but stretches far into the membrane. An allosteric modulator acting at this drug binding site would be specific for β2 subunit-containing GABAA receptors and an antagonist would block endocannabinoid action on GABAA receptors.

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