Figure 6
Molecular docking experiments reveal that top hits from screening FDA-approved drugs bind to allosteric sites. (a) Representive compounds, Salirasib and Candesartan, are shown bound to two identified allosteric sites adjacent to the active site looops (orange) in the closed conformation of PRL-3 (PDB: 2MBC). Lineweaver–burk plots indicate that Salirasib (b, c) and Candesartan (d, e) are non-competitive inhibitors to the substrate, supporting the docking results. Graphs in (c) and (e) are insets of the boxed areas in (b) and (d). Assays were run with technical duplicates and performed in 3 independent replicates. Error bars represent standard deviation between assays. Proposed binding modes of Salirasib (f) and Candesartan (g) on PRL-3, with residues in close proximity to the bound molecule identified.
