1OT7

Structural Basis for 3-deoxy-CDCA Binding and Activation of FXR

1OT7 の概要

• エントリーDOI: 10.2210/pdb1ot7/pdb
• 関連するPDBエントリー: 1OSV
• 分子名称: Bile Acid Receptor, dodecamer peptide fragment of RPGR-interacting protein 1, 6-ETHYL-CHENODEOXYCHOLIC ACID, ... (5 entities in total)
• 機能のキーワード: bile acid, nuclear receptor, coactivator, ligand binding domain, fxr, hormone-growth factor receptor complex, hormone/growth factor receptor
• 由来する生物種: Rattus norvegicus (Norway rat); 詳細
• 細胞内の位置: Nucleus (Probable): Q62735
• タンパク質・核酸の鎖数: 5
• 化学式量合計: 58712.76

構造登録者

Mi, L.Z.,Devarakonda, S.,Harp, J.M.,Han, Q.,Pellicciari, R.,Willson, T.M.,Khorasanizadeh, S.,Rastinejad, F. (登録日: 2003-03-21, 公開日: 2004-03-23, 最終更新日: 2024-04-03)

主引用文献

Mi, L.Z.,Devarakonda, S.,Harp, J.M.,Han, Q.,Pellicciari, R.,Willson, T.M.,Khorasanizadeh, S.,Rastinejad, F.
Structural Basis for Bile Acid Binding and Activation of the Nuclear Receptor FXR
Mol.Cell, 11:1093-1100, 2003

PubMed Abstract: The nuclear receptor FXR is the sensor of physiological levels of enterohepatic bile acids, the end products of cholesterol catabolism. Here we report crystal structures of the FXR ligand binding domain in complex with coactivator peptide and two different bile acids. An unusual A/B ring juncture, a feature associated with bile acids and no other steroids, provides ligand discrimination and triggers a pi-cation switch that activates FXR. Helix 12, the activation function 2 of the receptor, adopts the agonist conformation and stabilizes coactivator peptide binding. FXR is able to interact simultaneously with two coactivator motifs, providing a mechanism for enhanced binding of coactivators through intermolecular contacts between their LXXLL sequences. These FXR complexes provide direct insights into the design of therapeutic bile acids for treatment of hyperlipidemia and cholestasis.

PubMed: 12718893
DOI: 10.1016/S1097-2765(03)00112-6

実験手法

X-RAY DIFFRACTION (2.9 Å)