4cfl

N-TERMINAL BROMODOMAIN OF HUMAN BRD4 WITH LY303511

spinqualitylabelsall models 4cfl, resolution 1.32Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4cfl 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 1.32Å Ligands: 8DQ, EDO, GOL 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 A commonly used small-molecule probe in cell-signaling research is the phosphoinositide 3-kinase inhibitor LY294002. Quantitative chemoproteomic profiling shows that LY294002 and LY303511, a close analogue devoid of PI3K activity, inhibit the BET bromodomain proteins BRD2, BRD3, and BRD4 that comprise a family of targets structurally unrelated to PI3K. Both compounds competitively inhibit acetyl-lysine binding of the first but not the second bromodomain of BET proteins in cell extracts. X-ray crystallography shows that the chromen-4-one scaffold represents a new bromodomain pharmacophore and establishes LY294002 as a dual kinase and BET-bromodomain inhibitor, whereas LY303511 exhibits anti-inflammatory and antiproliferative effects similar to the recently discovered BET inhibitors. The Commonly Used PI3-Kinase Probe LY294002 Is an Inhibitor of BET Bromodomains.,Dittmann A, Werner T, Chung CW, Savitski MM, Falth Savitski M, Grandi P, Hopf C, Lindon M, Neubauer G, Prinjha RK, Bantscheff M, Drewes G ACS Chem Biol. 2014 Feb 21;9(2):495-502. doi: 10.1021/cb400789e. Epub 2013 Dec, 10. PMID:24533473 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Bromodomain-containing protein 3D structures

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