Figure 11

IDPs as drug targets. Protein-protein interactions involving α-helical or β-strand portion of the partners are used to design small molecules for cancer drugs. A. A ribbon diagram of complex of β-catenin (light colors) and T cell factor (red) was regenerated from PDB 1G3J. The structure of β-catenin is consisted of 12 tri-helical repeats (except the repeat 7, which just has two helical units). Small molecules from a natural-product library were screened and a couple of inhibitors were found. However, the binding sites for the small molecule inhibitors were not clear. B. A ribbon diagram of complex of MDM2 (green) and P53 fragment (red) was regenerated from PDB 1YCR. Small molecule inhibitors were designed based on the structure of the helical fragment of P53. C. A ribbon diagram of complex of Bcl-xL (green) and BAK fragment (red) was regenerated from PDB 1BXL. Small molecules were designed based on the 20-residue helix of BAK to inhibit the interaction. D. A ribbon diagram of complex of XIAP (green) and Smac fragment (red) was regenerated from PDB 1G3F. Small molecule inhibitors were designed based on the β-strand fragment (AVPIAQKSE) of Smac.