Extended Data Fig. 8: Detailed binding site and ligand pose analysis.
From: Structures of synaptic vesicle protein 2A and 2B bound to anticonvulsants
a. LigPlot of the UCB-2500 binding site in SV2A. Hydrogen bonds are depicted as green dashed lines. b. LigPlot of the PSL binding site in SV2B. Hydrogen bonds are depicted as green dashed lines. c. Comparison of two poses of UCB-2500 fit in the cryo-EM density. d. Comparison of two poses of PSL fit in the cryo-EM density. e. Perturbation map used to perform the FEP calculations. Similarities between pairs of ligands are shown in green f. 3H-UCB-J saturation binding experiments to wild-type and D670A (red squares) and W300A (blue triangles) SV2A, the data are mean ± s.e.m. Mutation of W300 or D670 to alanine abolishes 3H-UCB-J binding. The Kd of UCB-J was measured for wild-type SV2A (black circles, Kd = 1.5 ± 0.1 nM). g. BRV competition for wild type SV2B (black curve, Ki = 85 ± 22 uM), G240C (red curve, Ki = 80 ± 23 uM), and C600G (light blue curve, Ki = 149 ± 69 uM). Data shown in panels f,g are shown as mean ± s.e.m., exact values, the number of repeated independent experiments are reported in Supplementary Table 4.
