Surface conservation of the type II PAKs.

PAK6 in complex with PF-3758309 is shown with the surface of PAK6 protein colored blue for residues identical between human PAK4, PAK5 and PAK6, and white for non-conserved residues. PF-3758309 is shown in stick format with carbons shown yellow. The co-crystal structures of PAK6 with sunitinib and PAK4 in complex with its autoinhibitory pseudosubstrate [9] (PDB ID: 4FII) were superposed onto the PAK6/PF-3758309 structure and both sunitinib and the autoinhibitory pseudosubstrate inhibitor are shown. The carbon atoms of sunitinib are colored orange and the carbon atoms of the PAK4 autoinhibitory pseudosubstrate are colored pink. Residues adjacent to the kinase linker display differences between the type II PAK family, and are labeled and colored green. Kinase N- and C-lobes are indicated.