4CFK
N-TERMINAL BROMODOMAIN OF HUMAN BRD4 WITH LY294002
Summary for 4CFK
| Entry DOI | 10.2210/pdb4cfk/pdb |
| Related | 4CFL |
| Descriptor | BRD4 PROTEIN, GLYCEROL, 2-MORPHOLIN-4-YL-7-PHENYL-4H-CHROMEN-4-ONE, ... (5 entities in total) |
| Functional Keywords | cell cycle, inhibitor, histone, epigenetic reader, antagonist |
| Biological source | HOMO SAPIENS (HUMAN) |
| Total number of polymer chains | 1 |
| Total formula weight | 15560.88 |
| Authors | Chung, C.,Dittmann, A.,Drewes, G. (deposition date: 2013-11-18, release date: 2014-01-15, Last modification date: 2024-05-08) |
| Primary citation | Dittmann, A.,Werner, T.,Chung, C.,Savitski, M.M.,Falth Savitski, M.,Grandi, P.,Hopf, C.,Lindon, M.,Neubauer, G.,Prinjha, R.K.,Bantscheff, M.,Drewes, G. The Commonly Used Pi3-Kinase Probe Ly294002 is an Inhibitor of Bet Bromodomains. Acs Chem.Biol., 9:495-, 2014 Cited by PubMed Abstract: 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. PubMed: 24533473DOI: 10.1021/CB400789E PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.55 Å) |
Structure validation
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