Figure 3.

Binding of PP1 to wild-type MPK6, and NA-PP1 to the sensitized MPK6 variants, MPK6^YG.

NA-PP1, an analog of PP1 with bulky side chain, would have atomic clashes with the Tyr residue in the ATP binding pocket of wild-type MPK6, but not so with the sensitized MPK6^YG variants (right panel). In contrast, PP1 can access the ATP-binding pocket of wild-type kinases (left panels). The three-dimensional atomic structure of MPK6 was built based on the crystal structure of human ERK2 (PDB entry: 1WZY) using the MODELLER software. The three dimensional atomic structure of NA-PP1 was built using Chimera based on the crystal structure of PP1 (PDB entry: 2IVV). The binding mode of MPK6 with PP1, or the sensitized MPK6 (MPK6^YG) with NA-PP1 was produced by superimposing MPK6 or MPK6^YG with the crystal structure of RET tyrosine kinase bound with PP1 using Chimera software. In both panels, the protein is plotted in ribbon diagram. The backbones of Y144 in wild-type MPK6 and backbones of G144 in MPK6^YG are highlighted in red. The ligand and Y144 in MPK6 are displayed in stick mode and colored by atom types. Red: oxygens; blue: nitrogens, and grey: carbons. Hydrogen atoms are not shown.