Figure 11.

Crystal structures of the complexes of Keap1 with compounds (A) 1 (PDB ID: 6Z6A),⁹ (B) 60 (PDB ID: 7Q6S), (C) 63 (PDB ID: 7Q8R), and (D) 64 (PDB ID: 7Q96). Compound 1 is shown as teal sticks, while compounds 60, 63, and 64 are shown as orange, green, and magenta sticks, respectively. Keap1 is shown as a white surface with the oxygen atoms in red and nitrogen atoms in blue, selected Keap1 residues are shown as orange sticks, polar contacts are shown as yellow dashed lines, a chloride ion is shown as a green sphere, and bound water molecules are shown as red spheres. (E) Overlap of compounds 63 (green) and 64 (magenta) providing a close-up view of their polar contacts (yellow dashed lines) with R483 and S508. Keap1 (from PDB ID: 7Q96) is shown as a gray cartoon, with selected residues in the appropriate complex shown as sticks matching the color of the corresponding ligand. (F) Close-up view showing the orientations of residues R415, R483, and S508 of Keap1 in the complexes with compounds 1, 60, 63, and 64. The ligands have been removed for clarity, but the side chains of the three residues are colored as for each ligand in (panels A–D), i.e., teal (1), orange (60), green (63), and magenta (64). Keap1 (from PDB ID: 6Z6A) is shown as a gray cartoon.