Destabilization of the torsioned conformation of a ligand side chain inverts the LXRβ activity

LAUTARO D. ALVAREZ; M. VIRGINIA DANSEY; DIEGO Y GRINMAN; DANIELA NAVALESI; GISELA A SAMAJA; M CELESTE DEL FUEYO; NIEK BASTIAENSEN; RENÉ HOUTMAN; DARIO A ESTRIN; ADRIANA S VELEIRO; ADALI PECCI; GERARDO BURTON

BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS

ELSEVIER SCIENCE BV

Lugar: Amsterdam; Año: 2015 vol. 1851 p. 1577 - 1586

1388-1981

Liver X receptors (LXRs) are transcription factors activated by cholesterol metabolites containing an oxidized side chain. Due to their ability to regulate lipid metabolism and cholesterol transport, they have become attractive pharmacological targets. LXRs are closely related to DAF-12, a nuclear receptor involved in nematode lifespan and regulated by the binding of C-27 steroidal acids. Based on our recent finding that the lack of the C-25 methyl group does not abolish their DAF-12 activity, we evaluated the effect of removing it from the (25R)-cholestenoic acid, a LXR agonist.