Figure 7.

Noncompetitive inhibitor binding site and gating. (a) Crystal structure of GluA2 in the closed, resting state bound to the noncompetitive inhibitor perampanel (PMP) (GluA2_PMP, PDB entry 5L1F), with the ATD layer removed, viewed parallel to the membrane. The four PMP molecules bound in the ion channel extracellular collar are shown as space-filling models. (b) Close-up of the PMP binding site within GluA2_PMP subunit B. The PMP molecule is shown in ball-and-stick representation. (c) Close-up of the same region in the open state GluA2–STZ_Glu+CTZ structure. The green asterisk indicates the region where PMP binds in GluA2_PMP, which in the open state is occupied by the extracellular portion of M3 kinked at the A618 gating hinge.