Figure 5.

Structural basis for the constitutive activity – main ligand-binding pocket. The graphs show normalized concentration–response curves for AR231453 on selected receptors with mutations in the main ligand-binding pocket (black). On each graph, the wild-type curve is shown in stippled grey for comparison. The EC₅₀ values are indicated in grey stippled lines and can also be found in the upper left corner of each graph together with the surface expression level of the mutant and number of repetitions, except for graphs showing more than one mutant receptor – see Table 1. The helical wheel in the middle shows the location of the mutated residues, and a colour code denotes the level of constitutive activity obtained with the GPR119 receptor mutants. The colours are based on alanine substitutions. The constitutive activity was calculated by setting the E_max for AR231453-induced activation of the wild-type receptor to 100 and the mean value from cells transfected with an empty vector to 0.