4L7C

Structure of keap1 kelch domain with 2-{[(1S)-2-{[(1R,2S)-2-(1H-tetrazol-5-yl)cyclohexyl]carbonyl}-1,2,3,4-tetrahydroisoquinolin-1-yl]methyl}-1H-isoindole-1,3(2H)-dione

4L7C の概要

• エントリーDOI: 10.2210/pdb4l7c/pdb
• 関連するPDBエントリー: 4L7C 4L7D 4N1B
• 分子名称: Kelch-like ECH-associated protein 1, 2-{[(1S)-2-{[(1R,2S)-2-(1H-tetrazol-5-yl)cyclohexyl]carbonyl}-1,2,3,4-tetrahydroisoquinolin-1-yl]methyl}-1H-isoindole-1,3(2H)-dione, ACETATE ION, ... (4 entities in total)
• 機能のキーワード: stress sensor, kelch domain, kelch repeat motif, beta-propeller, nrf2, protein-small molecule complex, transcription-inhibitor complex, transcription/inhibitor
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Cytoplasm: Q14145
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 100736.19

構造登録者

Jnoff, E.,Brookfield, F.,Albrecht, C.,Barker, J.J.,Barker, O.,Beaumont, E.,Bromidge, S.,Brooks, M.,Ceska, T.,Courade, J.P.,Crabbe, T.,Duclos, S.,Fryatt, T.,Jigorel, E.,Kwong, J.,Sands, Z.,Smith, M.A. (登録日: 2013-06-13, 公開日: 2014-02-19, 最終更新日: 2024-10-30)

主引用文献

Jnoff, E.,Albrecht, C.,Barker, J.J.,Barker, O.,Beaumont, E.,Bromidge, S.,Brookfield, F.,Brooks, M.,Bubert, C.,Ceska, T.,Corden, V.,Dawson, G.,Duclos, S.,Fryatt, T.,Genicot, C.,Jigorel, E.,Kwong, J.,Maghames, R.,Mushi, I.,Pike, R.,Sands, Z.A.,Smith, M.A.,Stimson, C.C.,Courade, J.P.
Binding Mode and Structure-Activity Relationships around Direct Inhibitors of the Nrf2-Keap1 Complex.
Chemmedchem, 9:699-705, 2014

PubMed Abstract: An X-ray crystal structure of Kelch-like ECH-associated protein (Keap1) co-crystallised with (1S,2R)-2-[(1S)-1-[(1,3-dioxo-2,3-dihydro-1H-isoindol-2-yl)methyl]-1,2,3,4-tetrahydroisoquinolin-2-carbonyl]cyclohexane-1-carboxylic acid (compound (S,R,S)-1 a) was obtained. This X-ray crystal structure provides breakthrough experimental evidence for the true binding mode of the hit compound (S,R,S)-1 a, as the ligand orientation was found to differ from that of the initial docking model, which was available at the start of the project. Crystallographic elucidation of this binding mode helped to focus and drive the drug design process more effectively and efficiently.

PubMed: 24504667
DOI: 10.1002/cmdc.201300525

実験手法

X-RAY DIFFRACTION (2.4 Å)