Bile acid receptor

Function

Bile acid receptor or farnesoid X receptor (FXR) binds bile acids, then translocates to the nucleus, forms a dimer and binds to hormone response elements. This causes up- or down-regulation of certain genes involved in cholesterol metabolism, lipid homeostasis and absorption of fats and vitamins. FXR ligand-binding domain (LBD) binds chenodeoxycholic acid (CDC), lithocholic acid and deoxycholic acid. ^[1]

Disease

FXR is involved in pathophysiology of inflammatory bowel disease, colorectal cancer and type II diabetes.

Relevance

FXR and other bile acid receptors are targets for the treatment of dyslipidemia, diabetes and cardiovascular disease.

Structural highlights

of human FXR ligand-binding domain (deeppink) complex with non-steroidal agonist, nuclear receptor coactivator 1 peptide (cyan) and sulfate ions (PDB entry 3ruu). ^[2]

Structure of human FXR ligand-binding domain (magenta) complex with non-steroidal agonist, nuclear receptor coactivator 1 peptide (cyan) and sulfate ions (PDB entry 3ruu)

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3D structures of bile acid receptor3D structures of bile acid receptor

Updated on 30-November-2015

1osh, 3fli, 3l1b – hFXR LBD + non-steroidal agonist - human
1osv – hFXR LBD + CDC derivative + nuclear receptor coactivator 2 peptide
4ii6, 4wvd - hFXR LBD + nuclear receptor corepressor peptide
3bej, 3dct, 3dcu, 3hc5, 3hc6, 3rut, 3ruu, 3rvf – hFXR LBD + non-steroidal agonist + nuclear receptor coactivator 1 peptide
3fxv, 3gd2, 3okh, 3oki, 3olf, 3omk, 3omm, 3oof, 3ook, 3p88, 3p89 – hFXR LBD (mutant) + non-steroidal agonist + nuclear receptor coactivator 1 peptide
1ot7 – hFXR LBD + CDC derivative + RPGR-interacting protein peptide

ReferencesReferences

↑ Schaap FG, Trauner M, Jansen PL. Bile acid receptors as targets for drug development. Nat Rev Gastroenterol Hepatol. 2014 Jan;11(1):55-67. doi:, 10.1038/nrgastro.2013.151. Epub 2013 Aug 27. PMID:23982684 doi:http://dx.doi.org/10.1038/nrgastro.2013.151
↑ Akwabi-Ameyaw A, Caravella JA, Chen L, Creech KL, Deaton DN, Madauss KP, Marr HB, Miller AB, Navas F 3rd, Parks DJ, Spearing PK, Todd D, Williams SP, Wisely GB. Conformationally constrained farnesoid X receptor (FXR) agonists: Alternative replacements of the stilbene. Bioorg Med Chem Lett. 2011 Aug 11. PMID:21890356 doi:10.1016/j.bmcl.2011.08.034

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Michal Harel, Alexander Berchansky, Joel L. Sussman

[1] Schaap FG, Trauner M, Jansen PL. Bile acid receptors as targets for drug development. Nat Rev Gastroenterol Hepatol. 2014 Jan;11(1):55-67. doi:, 10.1038/nrgastro.2013.151. Epub 2013 Aug 27. PMID:23982684 doi:http://dx.doi.org/10.1038/nrgastro.2013.151

[2] Akwabi-Ameyaw A, Caravella JA, Chen L, Creech KL, Deaton DN, Madauss KP, Marr HB, Miller AB, Navas F 3rd, Parks DJ, Spearing PK, Todd D, Williams SP, Wisely GB. Conformationally constrained farnesoid X receptor (FXR) agonists: Alternative replacements of the stilbene. Bioorg Med Chem Lett. 2011 Aug 11. PMID:21890356 doi:10.1016/j.bmcl.2011.08.034

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