Figure 5.

PPARα/δ/γ-LBD–seladelpar cocrystal structures. Cocrystals of seladelpar and PPARα-LBD (A–C), PPARδ-LBD (D–F), or PPARγ-LBD (G–I) were analyzed using X-ray diffraction. (A,D,G) Overall structures of the complexes deposited in PDB with IDs 8HUN, 8HUO, and 8HUP, respectively. The SRC1 peptide (α-helix in magenta) and the AF-2 helix 12 (α-helix in red) are indicated by arrows (only in (G)) and arrowheads, respectively. The highest resolutions are labeled. (B,E,H) Magnified views of seladelpar located in the “Center” and the “Arm II” regions of PPARα/δ/γ-LBD. The electron density is shown in the mesh via F_o–F_c omit maps contoured at +3.0 σ. Water molecules are presented as cyan spheres in (B). (C,F,I) Hydrogen bonds and electrostatic interactions between seladelpar and the four consensus amino acid residues (that recognize the carboxyl moiety of seladelpar) are indicated by red and blue dotted lines, respectively, along with their distances (in Å). (J) Superposed view of seladelpar in PPARα (magenta)/PPARδ (green)/PPARγ (cyan)-LBD cocrystal structures.