FIGURE 4.

Structural similarity between DAF-12 and FXR LBDs. A, superposition of the AceDAF-12 LBD complex a (green) onto the FXR LBD (orange). (25S)-Δ7-DA is in white and the FXR ligand 6ECDCA is in blue. The ligand orientation is the same in FXR and DAF-12 but different from that in other nuclear receptors. Rings of the Δ7-DA steroid skeleton are labeled as A–D. B, amino acids involved in binding the carboxyl group of the ligand are conserved. C, H-bond interactions with the C3 end of the ligand are similar. FXR Tyr-358 H-bonds with the C3-hydroxyl group of 6ECDCA (red dashed line), and AceDAF-12 Gln-571 H-bonds with the C3-keto group of Δ7-DA (white dashed line) as seen in complex b.