3NSP
Crystal structure of tetrameric RXRalpha-LBD
3NSP の概要
| エントリーDOI | 10.2210/pdb3nsp/pdb |
| 関連するPDBエントリー | 3NSQ |
| 分子名称 | Retinoid X receptor, alpha (2 entities in total) |
| 機能のキーワード | nuclear receptor retinoic x recepor alpha ligand binding domain, transcription |
| 由来する生物種 | Homo sapiens (human) |
| タンパク質・核酸の鎖数 | 2 |
| 化学式量合計 | 53712.08 |
| 構造登録者 | |
| 主引用文献 | Zhang, H.,Zhou, R.,Li, L.,Chen, J.,Chen, L.,Li, C.,Ding, H.,Yu, L.,Hu, L.,Jiang, H.,Shen, X. Danthron functions as a retinoic X receptor antagonist by stabilizing tetramers of the receptor. J.Biol.Chem., 286:1868-1875, 2011 Cited by PubMed Abstract: Retinoic X receptor (RXR) is a promising target for drug discovery against cancer and metabolic syndromes. Here, we identified a specific RXRα antagonist, danthron, from the traditional Chinese medicine rhubarb. Danthron repressed all tested RXRα-involved response element transcription, including the RXRE, PPRE, FXRE, and LXRE. Results from native PAGE and isothermal titration calorimetry (ITC)-based assays indicated that danthron bound to the tetrameric RXRα-LBD in a specific stoichimetric ratio, and such a binding could influence the corepressor SMRT affinity to the receptor. Additionally, a unique tetrameric structure of the apo-RXRα ligand-binding domain (LBD) was determined, which exhibited a larger tetramer interface and different ligand-binding pocket size compared with the one previously reported. Together with the biochemical and biophysical results, the determined crystal structure of danthron-soaked RXRα-LBD suggested a new mechanism for danthron antagonism to tetrameric RXRα. Moreover, the in vivo efficient improvement of insulin sensitivity by danthron was observed in diet-induced obese (DIO) mice. Thus, our findings were expected to supply new insights into the structural basis of RXRα antagonist for its further potential therapeutic application. PubMed: 21084305DOI: 10.1074/jbc.M110.166215 主引用文献が同じPDBエントリー |
| 実験手法 | X-RAY DIFFRACTION (2.9 Å) |
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