5IXK

RORgamma in complex with inverse agonist BIO399.

Summary for 5IXK

• Entry DOI: 10.2210/pdb5ixk/pdb
• Descriptor: Nuclear receptor ROR-gamma, N-(5-ethyl-3,3-dimethyl-4-oxo-2,3,4,5-tetrahydro-1,5-benzoxazepin-8-yl)-3,4-dimethyl-N-(2,2,2-trifluoroethyl)benzene-1-sulfonamide (3 entities in total)
• Functional Keywords: rorgamma, nuclear hormone receptor, inverse agonist, af2 helix, immune system
• Biological source: Homo sapiens (Human)
• Cellular location: Nucleus : P51449
• Total number of polymer chains: 2
• Total formula weight: 54084.37

Authors

Marcotte, D.J. (deposition date: 2016-03-23, release date: 2016-06-15, Last modification date: 2023-09-27)

Primary citation

Marcotte, D.J.,Liu, Y.,Little, K.,Jones, J.H.,Powell, N.A.,Wildes, C.P.,Silvian, L.F.,Chodaparambil, J.V.
Structural determinant for inducing RORgamma specific inverse agonism triggered by a synthetic benzoxazinone ligand.
Bmc Struct.Biol., 16:7-7, 2016

PubMed Abstract: 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.

PubMed: 27246200
DOI: 10.1186/s12900-016-0059-3

Experimental method

X-RAY DIFFRACTION (2.35 Å)