4Q0A

Vitamin D Receptor complex with lithocholic acid

4Q0A の概要

• エントリーDOI: 10.2210/pdb4q0a/pdb
• 関連するPDBエントリー: 2HC4 2HCD
• 分子名称: Vitamin D3 receptor A, Nuclear receptor coactivator 2, (3beta,5beta,14beta,17alpha)-3-hydroxycholan-24-oic acid, ... (4 entities in total)
• 機能のキーワード: alpha-helical sandwich, transcription factor, calcitriol binding, dna binding, nucleus, gene regulation
• 由来する生物種: Danio rerio (leopard danio,zebra danio,zebra fish); 詳細
• 細胞内の位置: Nucleus: Q9PTN2 Q15596
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 36032.31

構造登録者

Belorusova, A.,Rochel, N. (登録日: 2014-04-01, 公開日: 2014-07-02, 最終更新日: 2024-02-28)

主引用文献

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

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: 24818857
DOI: 10.1021/jm5002524

実験手法

X-RAY DIFFRACTION (1.9 Å)