View larger version (48K):
[in this window]
[in a new window]
|
Fig. 4. PXR Ligand-Binding Pocket with Modeled 3-Keto-Lithocholic Acid and 5-ß-Pregnane-3,20-Dione
A, Analysis of the potential interactions between PXR and other endogenous ligands (as well as dexamethasone) predicted by the PXR-estradiol complex reported here. A schematic view of the proximity of key side chains adjacent to estradiol is shown at top (S247, R410, S208), along with several residues near the 17-OH moiety. Known PXR agonists with 3-keto, 3-ß-acetate, 3-ß-hydroxy, and 3- -hydroxy groups are all predicted to form favorable interactions with S247; as shown, further favorable interactions may be formed with additional PXR residues, including H407, R413, D205, and K204. B, The endogenous PXR activator 5-ß-pregnane-3,20-dione (magenta), modeled into the PXR ligand-binding pocket (red) using PXR-estradiol complex as a guide and viewed in the roughly same orientation as Fig. 3, may form polar interactions with Ser-247 and Arg-410. C, The endogenous PXR activator 3-keto-lithocholic acid (cyan), modeled into the PXR ligand-binding pocket (red) using PXR-estradiol complex as a guide and viewed in the roughly same orientation as Fig. 3, may form polar interactions with Ser-247, Glu-321, and Arg-410.
|
was omitted. Panel A appears below, and the correctly labeled panels B and C, along with the legend, appear on the following page. The printer regrets the error. 
