View source for 4cfl


==N-TERMINAL BROMODOMAIN OF HUMAN BRD4 WITH LY303511==
<StructureSection load='4cfl' size='340' side='right' caption='[[4cfl]], [[Resolution|resolution]] 1.32&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4cfl]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4CFL OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4CFL FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=8DQ:8-PHENYL-2-PIPERAZIN-1-YL-CHROMEN-4-ONE'>8DQ</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4cfk|4cfk]]</td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4cfl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4cfl OCA], [http://pdbe.org/4cfl PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4cfl RCSB], [http://www.ebi.ac.uk/pdbsum/4cfl PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4cfl ProSAT]</span></td></tr>
</table>
<div style="background-color:#fffaf0;">
== 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<ref>PMID:24533473</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4cfl" style="background-color:#fffaf0;"></div>

==See Also==
*[[Bromodomain-containing protein|Bromodomain-containing protein]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Human]]
[[Category: Chung, C]]
[[Category: Dittmann, A]]
[[Category: Drewes, G]]
[[Category: Antagonist]]
[[Category: Cell cycle]]
[[Category: Epigenetic reader]]
[[Category: Histone]]
[[Category: Inhibitor]]
[[Category: Kinase]]