6t7z | pdb_00006t7z

KEAP1 IN COMPLEX WITH COMPOUND 44

spinqualitylabelsall models 6t7z, resolution 2.00Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6t7z is a 2 chain structure with sequence from Homo sapiens and Synthetic construct. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2Å Ligands: 4FB, ACE, ACT, NH2 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function KEAP1_HUMAN Publication Abstract from PubMed Inhibition of KEAP1-NRF2 protein-protein interaction is considered a promising strategy to selectively and effectively activate NRF2, a transcription factor which is involved in several pathologies such as Huntington's disease (HD). A library of linear peptides based on the NRF2-binding motifs was generated on the nonapeptide lead Ac-LDEETGEFL-NH2 spanning residues 76-84 of the Neh2 domain of NRF2 with the aim to replace E78, E79 and E82 with non-acidic amino acids. A deeper understanding of the features and accessibility of the T80 subpocket was also targeted by structure-based design. Approaches to improve cell permeability were investigated using both different classes of cyclic peptides and conjugation to cell-penetrating peptides. This insight will guide future design of macrocycles, peptido-mimetics and, most importantly, small neutral brain-penetrating molecules to evaluate whether NRF2 activators have utility in HD. Optimization of linear and cyclic peptide inhibitors of KEAP1-NRF2 protein-protein interaction.,Colarusso S, De Simone D, Frattarelli T, Andreini M, Cerretani M, Missineo A, Moretti D, Tambone S, Kempf G, Augustin M, Steinbacher S, Munoz-Sanjuan I, Park L, Summa V, Tomei L, Bresciani A, Dominguez C, Toledo-Sherman L, Bianchi E Bioorg Med Chem. 2020 Aug 30;28(21):115738. doi: 10.1016/j.bmc.2020.115738. PMID:33065433 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Kelch-like protein 3D structures

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