TY - JOUR AU - Marcotte, Douglas J. AU - Liu, YuTing AU - Little, Kevin AU - Jones, John H. AU - Powell, Noel A. AU - Wildes, Craig P. AU - Silvian, Laura F. AU - Chodaparambil, Jayanth V. PY - 2016 DA - 2016/06/01 TI - Structural determinant for inducing RORgamma specific inverse agonism triggered by a synthetic benzoxazinone ligand JO - BMC Structural Biology SP - 7 VL - 16 IS - 1 AB - The nuclear hormone receptor RORγ regulates transcriptional genes involved in the production of the pro-inflammatory interleukin IL-17 which has been linked to autoimmune diseases such as rheumatoid arthritis, multiple sclerosis and inflammatory bowel disease. This transcriptional activity of RORγ is modulated through a protein-protein interaction involving the activation function 2 (AF2) helix on the ligand binding domain of RORγ and a conserved LXXLL helix motif on coactivator proteins. Our goal was to develop a RORγ specific inverse agonist that would help down regulate pro-inflammatory gene transcription by disrupting the protein protein interaction with coactivator proteins as a therapeutic agent. SN - 1472-6807 UR - https://doi.org/10.1186/s12900-016-0059-3 DO - 10.1186/s12900-016-0059-3 ID - Marcotte2016 ER -