4in4

Crystal structure of cpd 15 bound to Keap1 Kelch domain

spinqualitylabelsall models 4in4, resolution 2.59Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4in4 is a 3 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.59Å Ligands: 4ID, PO4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function KEAP1_HUMAN Publication Abstract from PubMed Keap1 binds to the Nrf2 transcription factor to promote its degradation, resulting in the loss of gene products that protect against oxidative stress. While cell-active small molecules have been identified that modify cysteines in Keap1 and effect the Nrf2 dependent pathway, few act through a non-covalent mechanism. We have identified and characterized several small molecule compounds that specifically bind to the Keap1 Kelch-DC domain as measured by NMR, native mass spectrometry and X-ray crystallography. One compound upregulates Nrf2 response genes measured by a luciferase cell reporter assay. The non-covalent inhibition strategy presents a reasonable course of action to avoid toxic side-effects due to non-specific cysteine modification. Small molecules inhibit the interaction of Nrf2 and the Keap1 Kelch domain through a non-covalent mechanism.,Marcotte D, Zeng W, Hus JC, McKenzie A, Hession C, Jin P, Bergeron C, Lugovskoy A, Enyedy I, Cuervo H, Wang D, Atmanene C, Roecklin D, Vecchi M, Vivat V, Kraemer J, Winkler D, Hong V, Chao J, Lukashev M, Silvian L Bioorg Med Chem. 2013 Jul 15;21(14):4011-9. doi: 10.1016/j.bmc.2013.04.019. Epub , 2013 Apr 19. PMID:23647822 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Kelch-like protein 3D structures

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