Fig. 3: Conivaptan recognition by V2R.

a Cross-section of the conivaptan-binding pocket in V2R. Conivaptan-bound V2R is in purple, conivaptan is in orange. b Comparison of the binding pose of conivaptan and tolvaptan. The movement direction of ECL1 in conivaptan-V2R relative to that in tolvaptan is indicated by a red dashed arrow. c 2D presentation of interactions between conivaptan and the binding pocket residues in V2R. The moieties of conivaptan and their interacting residues are indicated by different colors for clarity. d, f Detailed interactions between conivaptan and ligand-binding pocket residues in V2R. The hydrogen bond is highlighted with a cyan dashed line. e Effects of pocket residue mutations in V2R on the antagonistic activity of conivaptan. Data are presented as means ± SEM from three independent experiments conducted in triplicate. One-way ANOVA followed by Dunnett’s multiple comparisons test was used to determine the P values compared with the response of WT. *P < 0.05; **P < 0.01; ***P < 0.001 and ****P < 0.0001 were considered statistically significant. The exact P values are as follows: P = 0.0041 for I209^5.42A; P = 0.0002 for F288^6.52A; P = 0.4160 for Q291^6.55A; P = 0.1178 for F307^7.35A; P = 0.4099 for M311^7.39A; P < 0.0001 for F105^ECL1A, M120^3.33A, M123^3.36A, F178^4.64A, Y205^5.38A, V206^5.39A, and F287^6.51A.