THE BENZODIAZEPINE BINDING-SITE OF GABA(A) RECEPTORS

The GABA(A) receptor belongs, along with the nicotinic acetylcholine r eceptor, the glycine receptor arid the 5-HT3 receptor, to a family of homologous transmitter gated ion chann els mediating fast synaptic tra nsmission. Many classes of drug interact with the GABA(A) receptor, wh ich 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 r ecent studies that have identified amino acid residues that are though t to form the binding pocket for these compounds. These residues are p robably located at subunit interfaces of the protein pentamer and at l east some of them are homologous to residues implicated in channel ago nist binding. This implies pseudosymmetry of channel agonist and chann el modulatory sites, which may be, as recent data indicate, a general principle realized in other pseudosymmetric protein complexes.