UCSF

Structure of the general anaesthetic siteThe molecular mechanism of action of general anaesthetics is poorly understood, although there is some evidence that the principal protein targets are pentameric ligand-gated ion channel (pLGICs). The X-ray crystal structures of two common anaesthetics, propofol and desflurane, bound to a bacterial homolog of the pLGIC family have now been determined. The structures reveal that the two anaesthetics bind in the same site — in the upper part of the transmembrane domain of the channel — although desflurane binds deeper inside the ligand-binding cavity. It may be possible to use these structures to design new allosteric modulators that inhibit or potentiate pLGICs at the anaesthetic-binding site.