4x3s | pdb_00004x3s

Crystal structure of chromobox homology 7 (CBX7) with SETDB1-1170me3 Peptide

spinqualitylabelsall models 4x3s, resolution 1.60Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4x3s is a 4 chain structure with sequence from Homo sapiens and Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.6Å Ligands: CIT, FE, M3L Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function CBX7_MOUSE Component of a Polycomb group (PcG) multiprotein PRC1-like complex, a complex class required to maintain the transcriptionally repressive state of many genes, including Hox genes, throughout development. PcG PRC1 complex acts via chromatin remodeling and modification of histones; it mediates monoubiquitination of histone H2A 'Lys-119', rendering chromatin heritably changed in its expressibility. Promotes histone H3 trimethylation at 'Lys-9' (H3K9me3). Binds to histone H3 trimethylated 'Lys-9' (H3K9me3) or at 'Lys-27' (H3K27me3). May possibly also bind trimethylated lysine residues in other proteins (in vitro). Binds non-coding, single-stranded RNA. Regulator of cellular lifespan by maintaining the repression of CDKN2A, but not by inducing telomerase activity. Publication Abstract from PubMed Chromobox homolog 7 (CBX7) plays an important role in gene transcription in a wide array of cellular processes, ranging from stem cell self-renewal and differentiation to tumor progression. CBX7 functions through its N-terminal chromodomain (ChD), which recognizes trimethylated lysine 27 of histone 3 (H3K27me3), a conserved epigenetic mark that signifies gene transcriptional repression. In this study, we report the discovery of small molecules that inhibit CBX7ChD binding to H3K27me3. Our crystal structures reveal the binding modes of these molecules that compete against H3K27me3 binding through interactions with key residues in the methyl-lysine binding pocket of CBX7ChD. We further show that a lead compound, MS37452, derepresses transcription of Polycomb repressive complex target gene p16/CDKN2A by displacing CBX7 binding to the INK4A/ARF locus in prostate cancer cells. These small molecules have the potential to be developed into high-potency chemical modulators that target CBX7 functions in gene transcription in different disease pathways. Small-Molecule Modulators of Methyl-Lysine Binding for the CBX7 Chromodomain.,Ren C, Morohashi K, Plotnikov AN, Jakoncic J, Smith SG, Li J, Zeng L, Rodriguez Y, Stojanoff V, Walsh M, Zhou MM Chem Biol. 2015 Feb 19;22(2):161-8. doi: 10.1016/j.chembiol.2014.11.021. Epub, 2015 Feb 5. PMID:25660273 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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