4Q0A
Vitamin D Receptor complex with lithocholic acid
Summary for 4Q0A
| Entry DOI | 10.2210/pdb4q0a/pdb |
| Related | 2HC4 2HCD |
| Descriptor | Vitamin D3 receptor A, Nuclear receptor coactivator 2, (3beta,5beta,14beta,17alpha)-3-hydroxycholan-24-oic acid, ... (4 entities in total) |
| Functional Keywords | alpha-helical sandwich, transcription factor, calcitriol binding, dna binding, nucleus, gene regulation |
| Biological source | Danio rerio (leopard danio,zebra danio,zebra fish) More |
| Cellular location | Nucleus: Q9PTN2 Q15596 |
| Total number of polymer chains | 2 |
| Total formula weight | 36032.31 |
| Authors | Belorusova, A.,Rochel, N. (deposition date: 2014-04-01, release date: 2014-07-02, Last modification date: 2024-02-28) |
| Primary citation | Belorusova, A.Y.,Eberhardt, J.,Potier, N.,Stote, R.H.,Dejaegere, A.,Rochel, N. Structural insights into the molecular mechanism of vitamin d receptor activation by lithocholic Acid involving a new mode of ligand recognition. J.Med.Chem., 57:4710-4719, 2014 Cited by PubMed Abstract: The vitamin D receptor (VDR), an endocrine nuclear receptor for 1α,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. PubMed: 24818857DOI: 10.1021/jm5002524 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.9 Å) |
Structure validation
Download full validation report
