Fig. 1.
General anesthetic contacts within the γ-aminobutyric acid type A (GABAA) receptor β+–α− transmembrane cleft. The transmembrane domain of a α1β3γ2L structural homology model based on GluCl (Protein Data Bank 4COF) is depicted.25 Subunit peptide backbones are shown as ribbons (α1 = yellow; β3 = blue; γ2L = green), with sidechains of interest (table 1) shown in space-filling mode and labeled. Amino acid sidechains on β3-M3 and α1-M1 that are directly photolabeled by analogs of one or more study anesthetics are colored orange-red. Anesthetic contact sidechains that have previously been identified using substituted cysteine modification-protection are colored purple. Other β3-M2 and β3-M3 sidechains that line the β+–α− cleft, and three sidechains predicted to face the β3 intrasubunit helix bundle pocket (Y284, G287, and E298), are colored gray. The location of α1Q242 (pink) is also shown. Inserts display the molecular space-filling structures of propofol, etomidate, and alphaxalone, approximately scaled to the receptor model. Hydrogens have been hidden for clarity.