Figure 3.

β-Apo-13-carotenone is a high-affinity ligand for purified retinoic acid receptors and fits into the ligand-binding site: (A) competitive displacement of 5 nM tritiated atRA from purified RAR proteins by unlabeled atRA (filled diamond) as a positive control, β-apo-13-carotenone (filled triangle), 14′-CA (plus), 14′-AL (cross), and 13-cis-RA (filled square) as a negative control for the RARα (left) experiment, and CD 2665 (filled circle) and retinyl acetate (filled square) as a negative control for RARβ (middle) and RARγ (right) experiments; (B) binding affinities (in nM) of β-apocarotenoids to RARs calculated from the data shown in (A) and additional experiments with β-apo-12′-and β-apo-10′-carotenoic acids. For atRA and β-apo-13-carotenone, variance shown is for three independent experiments; (C) molecular modeling of the docking of atRA (red) and β-apo-13-carotenone (purple) into the ligand-binding site (protein backbone in green) of RARβ (PDB entry:1xap) (left). Shown on the right is the energy minimized then docked conformations of atRA (red) and β-apo-13-carotenone (purple) overlaid onto the conformation of the agonist TTNPB (white) as observed in the X-ray structure. Taken from reference [34] and used with permission.