Figure 3.

KcsA pore domain (green helices) with superimposed ligands from KcsA, GluR, NavAb, and CavAb channels. (A,B), Intracellular and intra-membrane views of the KcsA complex with tetradecylammonium (PDB ID: 2w0f). The ammonium nitrogen is at the focus of P-helices. Long decyl chains penetrate into subunit interfaces and reach the outer helices. Main channel contributors to the ligand-binding energy are shown by sticks. (C), 3D-aligned structures of TBA-bound KcsA (PDB ID: 2hvj) (green backbone and ligand carbons), MK801-bound NMDAR channel (PDB ID: 5un1) (orange backbone and ligand carbons), and IEM-1460 bound AMPAR channel (PDB ID: 6dm0) (cyan backbone and ligand carbons). The central cavity of the channels accommodates bulky moieties of TBA, MK801, and IEM-1460. Magenta spheres show potassium ions in Cd²⁺-bound KcsA (PDB ID: 3stl). The terminal ammonium group of IEM-1460 penetrates into the selectivity filter and binds near Site 3 of potassium ion; the second ammonium nitrogen binds close to the position of TBA ammonium nitrogen in KcsA. The ammonium group of MK801 binds in the central cavity, close to Site 5 of potassium ion KcsA. (D), Ammonium nitrogen atoms of cationic drugs (blue spheres) scatter over the central cavity.