Binding mode of 6ECDCA, a potent bile acid agonist of the farnesoid X receptor (FXR).
Based on the folding conservation across the nuclear receptor superfamily and the sequence homology with RAR-gamma, we report the construction of a three dimensional model of the ligand binding domain of FXR. The model is exploited for the elucidation of the binding mode of 6alpha-ethyl-chenodeoxycholic acid. The results of the docking experiments give quite clear indications that the bile acid derivative would bind the receptor in a mode significantly different than that observed for agonists of other nuclear receptor superfamily.
Costantino
Gabriele
G
Dipartimento di Chimica e Tecnologia del Farmaco, Università di Perugia, Via del Liceo 1, 06123 Perugia, Italy.
Macchiarulo
Antonio
A
Entrena-Guadix
Antonio
A
Camaioni
Emidio
E
Pellicciari
Roberto
R
D000595:Amino Acid Sequence; D001647:Bile Acids and Salts / Q000378:metabolism / Q000494:pharmacology; D001665:Binding Sites; D002635:Chenodeoxycholic Acid / Q000031:analogs & derivatives* / Q000378:metabolism* / Q000494:pharmacology*; D004268:DNA-Binding Proteins / Q000819:agonists* / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011485:Protein Binding; D018160:Receptors, Cytoplasmic and Nuclear; D018168:Receptors, Retinoic Acid / Q000235:genetics; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D014157:Transcription Factors / Q000819:agonists* / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D000099150:Receptor, Farnesoid X-Activated
D001647:Bile Acids and Salts; D002635:Chenodeoxycholic Acid; D004268:DNA-Binding Proteins; D018160:Receptors, Cytoplasmic and Nuclear; D018168:Receptors, Retinoic Acid; D014157:Transcription Factors; D000099150:Receptor, Farnesoid X-Activated; C464660:obeticholic acid