5eq0

Crystal Structure of chromodomain of CBX8 in complex with inhibitor UNC3866

spinqualitylabelsall models 5eq0, resolution 1.18Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5eq0 is a 2 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 1.18Å Ligands: 5R0, 5R5, ELY Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function CBX8_HUMAN Publication Abstract from PubMed We report the design and characterization of UNC3866, a potent antagonist of the methyllysine (Kme) reading function of the Polycomb CBX and CDY families of chromodomains. Polycomb CBX proteins regulate gene expression by targeting Polycomb repressive complex 1 (PRC1) to sites of H3K27me3 via their chromodomains. UNC3866 binds the chromodomains of CBX4 and CBX7 most potently, with a Kd of approximately 100 nM for each, and is 6- to 18-fold selective as compared to seven other CBX and CDY chromodomains while being highly selective over >250 other protein targets. X-ray crystallography revealed that UNC3866's interactions with the CBX chromodomains closely mimic those of the methylated H3 tail. UNC4195, a biotinylated derivative of UNC3866, was used to demonstrate that UNC3866 engages intact PRC1 and that EED incorporation into PRC1 is isoform dependent in PC3 prostate cancer cells. Finally, UNC3866 inhibits PC3 cell proliferation, consistent with the known ability of CBX7 overexpression to confer a growth advantage, whereas UNC4219, a methylated negative control compound, has negligible effects. A cellular chemical probe targeting the chromodomains of Polycomb repressive complex 1.,Stuckey JI, Dickson BM, Cheng N, Liu Y, Norris JL, Cholensky SH, Tempel W, Qin S, Huber KG, Sagum C, Black K, Li F, Huang XP, Roth BL, Baughman BM, Senisterra G, Pattenden SG, Vedadi M, Brown PJ, Bedford MT, Min J, Arrowsmith CH, James LI, Frye SV Nat Chem Biol. 2016 Mar;12(3):180-7. doi: 10.1038/nchembio.2007. Epub 2016 Jan, 25. PMID:26807715 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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