4mn3
From Proteopedia
Chromodomain antagonists that target the polycomb-group methyllysine reader protein Chromobox homolog 7 (CBX7)
Structural highlights
Function[CBX7_HUMAN] 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 trimethylated lysine residues in histones, and possibly also other proteins. Regulator of cellular lifespan by maintaining the repression of CDKN2A, but not by inducing telomerase activity.[1] [2] [3] [4] Publication Abstract from PubMedWe report here a peptide-driven approach to create first inhibitors of the chromobox homolog 7 (CBX7), a methyllysine reader protein. CBX7 uses its chromodomain to bind histone 3, lysine 27 trimethylated (H3K27me3), and this recognition event is implicated in silencing multiple tumor suppressors. Small trimethyllysine containing peptides were used as the basic scaffold from which potent ligands for disruption of CBX7-H3K27me3 complex were developed. Potency of ligands was determined by fluorescence polarization and/or isothermal titration calorimetry. Binding of one ligand was characterized in detail using 2D NMR and X-ray crystallography, revealing a structural motif unique among human CBX proteins. Inhibitors with a approximately 200 nM potency for CBX7 binding and 10-fold/400-fold selectivity over related CBX8/CBX1 proteins were identified. These are the first reported inhibitors of any chromodomain. Chromodomain Antagonists That Target the Polycomb-Group Methyllysine Reader Protein Chromobox Homolog 7 (CBX7).,Simhadri C, Daze KD, Douglas SF, Quon TT, Dev A, Gignac MC, Peng F, Heller M, Boulanger MJ, Wulff JE, Hof F J Med Chem. 2014 Mar 26. PMID:24625057[5] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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Categories: Human | Boulanger, M J | Chakravarthi, S | Daze, K | Dev, A | Douglas, S | Heller, M | Hof, F | Peng, F | Quon, T | Wulff, J | Chromobox domain 7 | Transcription regulator
