Abstract
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.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Amino Acid Sequence
-
Bile Acids and Salts / metabolism
-
Bile Acids and Salts / pharmacology
-
Binding Sites
-
Chenodeoxycholic Acid / analogs & derivatives*
-
Chenodeoxycholic Acid / metabolism*
-
Chenodeoxycholic Acid / pharmacology*
-
DNA-Binding Proteins / agonists*
-
DNA-Binding Proteins / chemistry
-
DNA-Binding Proteins / genetics
-
DNA-Binding Proteins / metabolism
-
Humans
-
Models, Molecular
-
Molecular Sequence Data
-
Protein Binding
-
Receptors, Cytoplasmic and Nuclear
-
Receptors, Retinoic Acid / genetics
-
Sequence Alignment
-
Sequence Homology, Amino Acid
-
Transcription Factors / agonists*
-
Transcription Factors / chemistry
-
Transcription Factors / genetics
-
Transcription Factors / metabolism
Substances
-
Bile Acids and Salts
-
DNA-Binding Proteins
-
Receptors, Cytoplasmic and Nuclear
-
Receptors, Retinoic Acid
-
Transcription Factors
-
obeticholic acid
-
farnesoid X-activated receptor
-
Chenodeoxycholic Acid