Fig. 9
Mechanism of inhibition for ifenprodil and 3-benzazepines. Mechanism of inhibition for ifenprodil and related 3-benzazepines at the ifenprodil binding site built by amino acids from the GluN1 ATD (purple) and the GluN2B R1 (green) and GluN2B R2 (cyan) subdomain. In active conformation phenyl moiety of GluN2B F176 (red) is orientated vertically and the GluN2B R2 subdomain is displaced preventing ligand binding. Transition from active to deactivated state results in repositioning of GluN2B R2 subdomain, moving α5 helix (red) downwards and subsequently reorient GluN2B F176 phenyl moiety to horizontal position enabling ligand binding. After compound binding to the receptor, backward movement of GluN2B F176 and α5 helix is inhibited resulting in structural coupling of GluN2B ATD subdomains with the GluN1 ATD, which prevents opposing movements resulting in locked receptor conformation
