Extended Data Fig. 9: Molecular mechanism of PYD-106 selectivity on N1-N2C di-receptors.
From: Distinct structure and gating mechanism in diverse NMDA receptors with GluN2C and GluN2D subunits
a, Structural formula of PYD-106 with the only chiral carbon atom in the molecule marked with a red asterisk and the fits of (R)- and (S)-PYD-106 into the EM map which is shown in mesh. Red arrows indicate the unfavorable fitting for (S)-PYD-106. b, Sequence alignment of Rat norvegicus N2A, N2B, N2C and N2D subunits. Red boxes indicate the homologous residues at the bottom of the R2 lobe and the top of the D1 lobe, which directly interact with PYD-106 in Ligplot+ in N2C (chain B). Three key residues that form hydrogen bonds with PYD-106 in N2C (R194, D220 and S472) and their homologous residues are highlighted in red. c, Comparison of the NTD-LBD interfaces of N2 subunits in N1-N2C, N1-N2A (PDB:6MMP, ref. 22), N1-N2B (PDB:7EU8, ref. 26) and N1-N2D di-receptors. The hydrophobicity feature of NTD-LBD interface is highlighted with residues at R2 and D1 lobes.
