6FMQ

Keap1 - peptide complex

6FMQ の概要

• エントリーDOI: 10.2210/pdb6fmq/pdb
• 分子名称: Kelch-like ECH-associated protein 1, ACY-SC1-GLU-THR-GLY-GLU-LEU, 1,2-ETHANEDIOL, ... (6 entities in total)
• 機能のキーワード: keap1, kelch-domain, nrf2, neurodegenerative, inhibitor, peptide binding protein
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 93316.82

構造登録者

Talapatra, S.K.,Kozielski, F.,Wells, G.,Georgakopoulos, N.D. (登録日: 2018-02-02, 公開日: 2018-08-08, 最終更新日: 2024-01-17)

主引用文献

Georgakopoulos, N.D.,Talapatra, S.K.,Gatliff, J.,Kozielski, F.,Wells, G.
Modified Peptide Inhibitors of the Keap1-Nrf2 Protein-Protein Interaction Incorporating Unnatural Amino Acids.
Chembiochem, 19:1810-1816, 2018

PubMed Abstract: Noncovalent inhibitors of the Keap1-Nrf2 protein-protein interaction (PPI) have therapeutic potential in a range of disease states including neurodegenerative diseases (Parkinson's and Alzheimer's diseases), chronic obstructive pulmonary disease and various inflammatory conditions. By stalling Keap1-mediated ubiquitination of Nrf2, such compounds can enhance Nrf2 transcriptional activity and activate the expression of a range of genes with antioxidant response elements in their promoter regions. Keap1 inhibitors based on peptide and small-molecule templates have been identified. In this paper we develop the structure-activity relationships of the peptide series and identify a group of ligands incorporating unnatural amino acids that demonstrate improved binding affinity in fluorescence polarisation, differential scanning fluorimetry and isothermal titration calorimetry assays. These modified peptides have the potential for further development into peptidomimetic chemical probes to explore the role of Nrf2 in disease and as potential lead structures for drug development.

PubMed: 29927029
DOI: 10.1002/cbic.201800170

実験手法

X-RAY DIFFRACTION (2.1 Å)