4Q0A: Vitamin D Receptor Complex With Lithocholic Acid

The vitamin D receptor (VDR), an endocrine nuclear receptor for 1alpha,25-dihydroxyvitamin D3, acts also as a bile acid sensor by binding lithocholic acid (LCA). The crystal structure of the zebrafish VDR ligand binding domain in complex with LCA and the SRC-2 coactivator peptide reveals the binding of two LCA molecules by VDR. One LCA binds to the canonical ligand-binding pocket, and the second one, which is not fully buried, is anchored to a site located on the VDR surface. Despite the low affinity of the alternative site, the binding of the second molecule promotes stabilization of the active receptor conformation. Biological activity assays, structural analysis, and molecular dynamics simulations indicate that the recognition of two ligand molecules is crucial for VDR agonism by LCA. The unique binding mode of LCA provides clues for the development of new chemical compounds that target alternative binding sites for therapeutic applications.
PDB ID: 4Q0ADownload
MMDB ID: 121227
PDB Deposition Date: 2014/4/1
Updated in MMDB: 2014/07
Experimental Method:
x-ray diffraction
Resolution: 1.9  Å
Source Organism:
Homo sapiens
Similar Structures:
Biological Unit for 4Q0A: dimeric; determined by author and by software (PISA)
Molecular Components in 4Q0A
Label Count Molecule
Proteins (2 molecules)
Vitamin D3 Receptor a(Gene symbol: vdra)
Molecule annotation
Nuclear Receptor Coactivator 2(Gene symbol: NCOA2)
Molecule annotation
Chemicals (2 molecules)
* Click molecule labels to explore molecular sequence information.

Citing MMDB