Fig. 3: Validation of key residues for ligand binding and isoform specificity. | Nature Communications

Fig. 3: Validation of key residues for ligand binding and isoform specificity.

From: Crystal structures of Ryanodine Receptor reveal dantrolene and azumolene interactions guiding inhibitor development

Fig. 3: Validation of key residues for ligand binding and isoform specificity.

A–C ITC binding isotherms showing the interaction of DAN with the R12 domain of RyR1 harboring the W995A (A), W881A (B), L969M, and L983M (C) mutations. The affinity and thermodynamic parameters are listed in Supplementary Table 1. D Superposition of the R12 domains from RyR1 (plum) and RyR2 (white). Homology models for both domains were generated using the RyR3 R12/DAN/AMP-PCP crystal structure as a template. Residues conserved between RyR1 and RyR3 but nonconserved in RyR2 are displayed, with key residues critical for isoform specificity, Leu983 and Leu969, highlighted in red.

Back to article page