5x54

Crystal structure of the Keap1 Kelch domain in complex with a tetrapeptide

spinqualitylabelsall models 5x54, resolution 2.30Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5x54 is a 4 chain structure with sequence from Escherichia phage T7 and Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.3Å Ligands: ACE, ACT Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function KEAP1_HUMAN Publication Abstract from PubMed Keap1 constitutively binds to the transcription factor Nrf2 to promote its degradation, resulting in negative modulation of genes involved in cellular protection against oxidative stress. Keap1 is increasingly recognized as an attractive target for treating diseases involving oxidative stress, including cancer, atherosclerosis, diabetes, arthritis, and neurodegeneration. We used phage-display peptide screening to identify a tetrapeptide showing moderate binding affinity, which inhibits the interaction between Nrf2 and Keap1. The tetrapeptide does not include an ETGE motif, which is a commonly found consensus sequence in known peptidic inhibitors. In addition to affinity parameters, IC50, KD, and thermodynamic parameters, the crystal structure of the complex was determined to elucidate the binding conformation. The binding interactions resemble those of known small-molecule inhibitors as opposed to those of substrates and peptidic inhibitors. Although the tetrapeptide's affinity is not very high, our results may help facilitate the designing of small-molecule inhibitors during lead generation in drug discovery. Discovery of a Kelch-like ECH-associated protein 1-inhibitory tetrapeptide and its structural characterization.,Sogabe S, Sakamoto K, Kamada Y, Kadotani A, Fukuda Y, Sakamoto JI Biochem Biophys Res Commun. 2017 Mar 14. pii: S0006-291X(17)30495-3. doi:, 10.1016/j.bbrc.2017.03.038. PMID:28315327 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Kelch-like protein 3D structures

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