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The benzodiazepine binding site of GABAA receptors

1997; Elsevier BV; Volume: 18; Issue: 4 Linguagem: Inglês

10.1016/s0165-6147(97)90675-1

1873-3735

Erwin Sigel, Andreas Buhr,

Ion channel regulation and function

Abstract The GABA A receptor belongs, along with the nicotinic acetylcholine receptor, the glycine receptor and the 5-HT 3 receptor, to a family of homologous transmitter-gated ion channels mediating fast synaptic transmission. Many classes of drug interact with the GABA A receptor, which is the major inhibitory ion channel in the mammalian brain. Among these drugs are the allosteric modulators acting at the benzodiazepine binding site. In this article, Erwin Sigel and Andreas Buhr discuss recent studies that have identified amino acid residues that are thought to form the binding pocket for these compounds. These residues are probably located at subunit interfaces of the protein pentamer and at least some of them are homologous to residues implicated in channel agonist binding. This implies pseudosymmetry of channel agonist and channel modulatory sites, which may be, as recent data indicate, a general principle realized in other pseudosymmetric protein complexes.