title: Two neighboring residues of loop A of the alpha1 subunit point towards the benzodiazepine binding site of GABAA receptors.
abstract: Benzodiazepines are widely used drugs exerting sedative, anxiolytic, muscle relaxant, and anticonvulsant effects by acting through specific high affinity binding sites on some GABA(A) receptors. It is important to understand how these ligands are positioned in this binding site. We are especially interested here in the conformation of loop A of the alpha(1)beta(2)gamma(2) GABA(A) receptor containing a key residue for the interaction of benzodiazepines: alpha(1)H101. We describe a direct interaction of alpha(1)N102 with a diazepam- and an imidazobenzodiazepine-derivative. Our observations help to better understand the conformation of this region of the benzodiazepine pocket in GABA(A) receptor.
authors.affiliation: Institute of Biochemistry and Molecular Medicine, University of Bern, Bühlstrasse 28, CH-3012 Bern, Switzerland.
authors.forename: Kelly R
authors.initials: KR
authors.lastname: Tan
authors.forename: Roland
authors.initials: R
authors.lastname: Baur
authors.forename: Anne
authors.initials: A
authors.lastname: Gonthier
authors.forename: Maurice
authors.initials: M
authors.lastname: Goeldner
authors.forename: Erwin
authors.initials: E
authors.lastname: Sigel
mesh_terms: D000494:Allosteric Regulation; D001216:Asparagine / Q000235:genetics / Q000378:metabolism; D001569:Benzodiazepines / Q000737:chemistry / Q000494:pharmacology*; D001665:Binding Sites; D002460:Cell Line; D006801:Humans; D008024:Ligands; D015394:Molecular Structure; D009154:Mutation / Q000235:genetics; D010649:Phenylalanine / Q000235:genetics / Q000378:metabolism; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism; D011963:Receptors, GABA-A / Q000235:genetics / Q000378:metabolism*
chemical_list: D008024:Ligands; D021122:Protein Subunits; D011963:Receptors, GABA-A; D001569:Benzodiazepines; D010649:Phenylalanine; D001216:Asparagine