A) Overall structure of PAK6 in complex with PF-3758309. PAK6 shown in cartoon format in cyan, PF-3758309 shown in stick format with carbons shown yellow. PAK6 N-lobe, C-lobe, activation loop, C-helix and P-loop are labeled. N- and C- termini are indicated. Phosphorylated activation loop serine, pS560, is shown in stick format and labeled. B) Overall structure of PAK6 in complex with sunitinib. PAK6 is colored purple and carbon atoms of sunitinib are colored orange. Global structural features are as indicated in A. C) Superposition of PAK6 with PF-3758309 and PAK6 with sunitinib. Slight conformational differences are observed in the glycine-rich P-loop, the C-helix and the orientation of the N-lobe. Superposition is of the kinase domain the C-lobes. D) Superposition of PAK6 with PF-3758309, PAK6 with sunitinib and apo PAK6. Crystal structure of Apo PAK6 [29] (PDB ID: 2C30) superposed onto the two inhibitor-bound PAK6 structures. Significant conformational movements are observed in the N-lobe particularly around the glycine-rich P-loop and the C-helix. Boxed area indicates the zoomed region shown in E. E) Close up highlighting the conformational differences between the PAK6 structures. A kink in the C-helix is clearly visible for the PF-3758309 and sunitinib-bound structures, indicated with an arrow. All structural figures generated using CCP4mg [46].