5EC9

Retinoic acid receptor alpha in complex with chiral dihydrobenzofuran benzoic acid 9a and a fragment of the coactivator TIF2

5EC9 の概要

• エントリーDOI: 10.2210/pdb5ec9/pdb
• 分子名称: Retinoic acid receptor RXR-alpha, LYS-HIS-LYS-ILE-LEU-HIS-ARG-LEU-LEU-GLN-ASP, 4-[(11S,15R)-4,4,7,7-Tetramethyl-16-oxatetracyclo[8.6.0.03,8.011,15]hexadeca-1(10),2,8-trien-11-yl]benzoic acid, ... (4 entities in total)
• 機能のキーワード: transcription, nuclear receptor, agonist
• 由来する生物種: Homo sapiens (Human); 詳細
• 細胞内の位置: Nucleus : P19793
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 25460.84

構造登録者

Leysen, S.,Ottmann, C.,Schafer, A.,Scheepstra, M.,Brunsveld, L.,Sunden, R.,Ma, J.N.,Burnstein, E.S.,Olsson, R. (登録日: 2015-10-20, 公開日: 2016-03-09, 最終更新日: 2024-06-19)

主引用文献

Sunden, H.,Schafer, A.,Scheepstra, M.,Leysen, S.,Malo, M.,Ma, J.N.,Burstein, E.S.,Ottmann, C.,Brunsveld, L.,Olsson, R.
Chiral Dihydrobenzofuran Acids Show Potent Retinoid X Receptor-Nuclear Receptor Related 1 Protein Dimer Activation.
J.Med.Chem., 59:1232-1238, 2016

PubMed Abstract: The nuclear receptor Nurr1 can be activated by RXR via heterodimerization (RXR-Nurr1) and is a promising target for treating neurodegenerative diseases. We herein report the enantioselective synthesis and SAR of sterically constricted benzofurans at RXR. The established SAR, using whole cell functional assays, lead to the full agonist 9a at RXR (pEC50 of 8.2) and RXR-Nurr1. The X-ray structure shows enantiomeric discrimination where 9a optimally addresses the ligand binding pocket of RXR.

PubMed: 26820900
DOI: 10.1021/acs.jmedchem.5b01702

実験手法

X-RAY DIFFRACTION (2.3 Å)