1XNX

Crystal structure of constitutive androstane receptor

Summary for 1XNX

• Entry DOI: 10.2210/pdb1xnx/pdb
• Descriptor: constitutive androstane receptor, 16,17-ANDROSTENE-3-OL (3 entities in total)
• Functional Keywords: nuclear receptor; crystal structure, ligand receptor-transcription regulation complex, ligand receptor/transcription regulation
• Biological source: Mus musculus (house mouse)
• Cellular location: Nucleus: O35627
• Total number of polymer chains: 2
• Total formula weight: 59843.34

Authors

Fernandez, E. (deposition date: 2004-10-05, release date: 2005-01-04, Last modification date: 2024-10-30)

Primary citation

Shan, L.,Vincent, J.,Brunzelle, J.S.,Dussault, I.,Lin, M.,Ianculescu, I.,Sherman, M.A.,Forman, B.M.,Fernandez, E.
Structure of the murine constitutive androstane receptor complexed to androstenol; a molecular basis for inverse agonism
Mol.Cell, 16:907-917, 2004

PubMed Abstract: The nuclear receptor CAR is a xenobiotic responsive transcription factor that plays a central role in the clearance of drugs and bilirubin while promoting cocaine and acetaminophen toxicity. In addition, CAR has established a "reverse" paradigm of nuclear receptor action where the receptor is active in the absence of ligand and inactive when bound to inverse agonists. We now report the crystal structure of murine CAR bound to the inverse agonist androstenol. Androstenol binds within the ligand binding pocket, but unlike many nuclear receptor ligands, it makes no contacts with helix H12/AF2. The transition from constitutive to basal activity (androstenol bound) appears to be associated with a ligand-induced kink between helices H10 and H11. This disrupts the previously predicted salt bridge that locks H12 in the transcriptionally active conformation. This mechanism of inverse agonism is distinct from traditional nuclear receptor antagonists thereby offering a new approach to receptor modulation.

PubMed: 15610734
DOI: 10.1016/j.molcel.2004.11.037

Experimental method

X-RAY DIFFRACTION (2.9 Å)