Figure 5.

Model of active site of PHLPP2 docked with substrate or inhibitors. (a) pNPP, (b) a phosphopeptide based on the hydrophobic motif of Akt (HFPQFpSYSAS, where the phosphorylated Ser corresponds to Ser473); (c) compound 7, (d) compound 4, and (f) compound 13 were docked in the PHLPP2 model 4. Ligands are represented in tube format, Mn²⁺ ions are represented as yellow spheres, and surface representation of PHLPP2 shows the electrostatic potential where blue represents positive, white neutral, and red negative electrostatic potential. Docked substrates or inhibitors are in green, the phosphate groups are highlighted in purple. * denotes the carbonyl group of Gly 745 in all views. (e) Lineweaver−Burke analysis of inhibition mechanism of compound 7. The activity of PHLPP was measured at eight different concentrations of pNPP in the presence of DMSO (gray solid circle), 5 μM (solid square), 10 μM (gray solid square), or 30 μM (open square) compound 7.