4qb3

Crystal structure of the first bromodomain of human BRD4 in complex with Olinone

spinqualitylabelsall models 4qb3, resolution 0.94Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4qb3 is a 1 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 0.94Å Ligands: 30M, EDO Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease BRD4_HUMAN Note=A chromosomal aberration involving BRD4 is found in a rare, aggressive, and lethal carcinoma arising in midline organs of young people. Translocation t(15;19)(q14;p13) with NUT which produces a BRD4-NUT fusion protein. Function BRD4_HUMAN Plays a role in a process governing chromosomal dynamics during mitosis (By similarity). Publication Abstract from PubMed Lysine acetylation regulates gene expression through modulating protein-protein interactions in chromatin. Chemical inhibition of acetyl-lysine binding bromodomains of the major chromatin regulators BET (bromodomain and extraterminal domain) proteins has been shown to effectively block cell proliferation in cancer and inflammation. However, whether selective inhibition of individual BET bromodomains has distinctive functional consequences remains only partially understood. In this study, we show that selective chemical inhibition of the first bromodomain of BET proteins using our small-molecule inhibitor, Olinone, accelerated the progression of mouse primary oligodendrocyte progenitors toward differentiation, whereas inhibition of both bromodomains of BET proteins hindered differentiation. This effect was target specific, as it was not detected in cells treated with inactive analogs and independent of any effect on proliferation. Therefore, selective chemical modulation of individual bromodomains, rather than use of broad-based inhibitors, may enhance regenerative strategies in disorders characterized by myelin loss such as aging and neurodegeneration. Selective chemical modulation of gene transcription favors oligodendrocyte lineage progression.,Gacias M, Gerona-Navarro G, Plotnikov AN, Zhang G, Zeng L, Kaur J, Moy G, Rusinova E, Rodriguez Y, Matikainen B, Vincek A, Joshua J, Casaccia P, Zhou MM Chem Biol. 2014 Jul 17;21(7):841-54. doi: 10.1016/j.chembiol.2014.05.009. Epub, 2014 Jun 19. PMID:24954007 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Bromodomain-containing protein 3D structures

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