6FMQ

Keap1 - peptide complex

Summary for 6FMQ

• Entry DOI: 10.2210/pdb6fmq/pdb
• Descriptor: Kelch-like ECH-associated protein 1, ACY-SC1-GLU-THR-GLY-GLU-LEU, 1,2-ETHANEDIOL, ... (6 entities in total)
• Functional Keywords: keap1, kelch-domain, nrf2, neurodegenerative, inhibitor, peptide binding protein
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 3
• Total formula weight: 93316.82

Authors

Talapatra, S.K.,Kozielski, F.,Wells, G.,Georgakopoulos, N.D. (deposition date: 2018-02-02, release date: 2018-08-08, Last modification date: 2024-01-17)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.1 Å)