1ILH

Crystal Structure of Human Pregnane X Receptor Ligand Binding Domain Bound to SR12813

1ILH の概要

• エントリーDOI: 10.2210/pdb1ilh/pdb
• 関連するPDBエントリー: 1ILG
• 分子名称: ORPHAN NUCLEAR RECEPTOR PXR, [2-(3,5-DI-TERT-BUTYL-4-HYDROXY-PHENYL)-1-(DIETHOXY-PHOSPHORYL)-VINYL]-PHOSPHONIC ACID DIETHLYL ESTER (3 entities in total)
• 機能のキーワード: nuclear receptor, multiple binding modes, xenobiotic, promiscuous, ligand, gene regulation
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Nucleus : O75469
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 36785.40

構造登録者

Watkins, R.E.,Redinbo, M.R. (登録日: 2001-05-08, 公開日: 2001-06-27, 最終更新日: 2023-08-16)

主引用文献

Watkins, R.E.,Wisely, G.B.,Moore, L.B.,Collins, J.L.,Lambert, M.H.,Williams, S.P.,Willson, T.M.,Kliewer, S.A.,Redinbo, M.R.
The human nuclear xenobiotic receptor PXR: structural determinants of directed promiscuity.
Science, 292:2329-2333, 2001

PubMed Abstract: The human nuclear pregnane X receptor (hPXR) activates cytochrome P450-3A expression in response to a wide variety of xenobiotics and plays a critical role in mediating dangerous drug-drug interactions. We present the crystal structures of the ligand-binding domain of hPXR both alone and in complex with the cholesterol-lowering drug SR12813 at resolutions of 2.5 and 2.75 angstroms, respectively. The hydrophobic ligand-binding cavity of hPXR contains a small number of polar residues, permitting SR12813 to bind in three distinct orientations. The position and nature of these polar residues were found to be critical for establishing the precise pharmacologic activation profile of PXR. Our findings provide important insights into how hPXR detects xenobiotics and may prove useful in predicting and avoiding drug-drug interactions.

PubMed: 11408620
DOI: 10.1126/science.1060762

実験手法

X-RAY DIFFRACTION (2.76 Å)