Mapping the binding of GluN2B-selective N-methyl-D-aspartate receptor negative allosteric modulators.

ABSTRACT: We have used recent structural advances in our understanding of the N-methyl-d-aspartate (NMDA) receptor amino terminal domain to explore the binding mode of multiple diaryl GluN2B-selective negative allosteric modulators at the interface between the GluN1 and GluN2B amino-terminal domains. We found that interaction of the A ring within the binding pocket seems largely invariant for a variety of structurally distinct ligands. In addition, a range of structurally diverse linkers between the two aryl rings can be accommodated by the binding site, providing a potential opportunity to tune interactions with the ligand binding pocket via changes in hydrogen bond donors, acceptors, as well as stereochemistry. The most diversity in atomic interactions between protein and ligand occur in the B rin

SUBMITTER: Burger PB 

PROVIDER: S-EPMC3400845 | biostudies-literature | 2012 Aug

REPOSITORIES: biostudies-literature