Fig. 4: Comparative interactions of GABAB and GABAA receptors with phosphinic acid inhibitors.
From: Cryo-EM structures of ρ1 GABAA receptors with antagonist and agonist drugs
a Chemical structure of CGP35348 (above) and its binding site in a human GABAB receptor (PDB ID 4MR8, green, below). The ligand (gray) and its direct residue contacts are colored by heteroatom. b Chemical structure of CGP36742 (above), and its superimposition into the equivalent GABAB-receptor site as in (a). The ligand pose is adopted from the structure reported here with ρ1-EM, aligned on the shared aminopropyl and phosphinic acid moieties of CGP35348. c Overview of the ECD of the human GABAB receptor as shown in (a). d Alignment of CGP36742 in ρ1-EM (tan) with CGP35348 in the GABAB receptor (gray) as implemented in b, colored by heteroatom. e Alignment of (S)−4-ACPBPA (tan) into the CGP36742 site of ρ1-EM. For perspective, principal and complementary subunits of ρ1-EM are colored purple and pink respectively; the ligand and interacting residues are colored by heteroatom. f Alignment of (S)−4-ACPBPA (tan) into the CGP35348 of the GABAB receptor site (green) shown in a. Dashed circle indicates prospective clash with residue W65.
