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. 2017 Jul 8;8(33):55147–55161. doi: 10.18632/oncotarget.19101

Figure 4. Ac-LA binds to the AKT PH domain and the ATP-binding site and inhibits the kinase activity of AKT.

Figure 4

(A) Predicted binding mode of ac-LA to the PH domain of Akt1 (PDB ID: 1H10, grey sticks: carbon, red sticks: oxygen, blue sticks: nitrogen, red dotted line: hydrogen bonds, atoms with negative partial charge are red, atoms with positive partial charge are blue). Ac-LA and lupeol are shown in green. Table shows the calculated binding energy of ac-LA to the PH domain and the ATP-binding site compared to that of lupeol and Akt inhibitor VIII. (B) Ac-LA inhibits the kinase activity of human recombinant Akt1, Akt2, and Akt3 more efficiently than lupeol. Akt inhibitor III (10 μM) was used as positive control, GSK-3 - substrate. (C) AKT1 lacking the PH domain (Akt1ΔPH) is less sensitive to ac-LA as analyzed in a kinase assay using GSK-3 as substrate. 32P-labelled substrate in (B and C) was scanned using a PhosphorImager. All data are representative of at least three independent experiments.