4o7c: Difference between revisions
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==Crystal structure of the first bromodomain of human BRD4 in complex with SB-614067-R== | ==Crystal structure of the first bromodomain of human BRD4 in complex with SB-614067-R== | ||
<StructureSection load='4o7c' size='340' side='right' caption='[[4o7c]], [[Resolution|resolution]] 1.55Å' scene=''> | <StructureSection load='4o7c' size='340' side='right' caption='[[4o7c]], [[Resolution|resolution]] 1.55Å' scene=''> | ||
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<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4o70|4o70]], [[4o71|4o71]], [[4o72|4o72]], [[4o73|4o73]], [[4o74|4o74]], [[4o75|4o75]], [[4o76|4o76]], [[4o77|4o77]], [[4o78|4o78]], [[4o7a|4o7a]], [[4o7b|4o7b]], [[4o7e|4o7e]], [[4o7f|4o7f]]</td></tr> | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4o70|4o70]], [[4o71|4o71]], [[4o72|4o72]], [[4o73|4o73]], [[4o74|4o74]], [[4o75|4o75]], [[4o76|4o76]], [[4o77|4o77]], [[4o78|4o78]], [[4o7a|4o7a]], [[4o7b|4o7b]], [[4o7e|4o7e]], [[4o7f|4o7f]]</td></tr> | ||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">BRD4, HUNK1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">BRD4, HUNK1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=4o7c FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4o7c OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4o7c RCSB], [http://www.ebi.ac.uk/pdbsum/4o7c PDBsum]</span></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=4o7c FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4o7c OCA], [http://pdbe.org/4o7c PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4o7c RCSB], [http://www.ebi.ac.uk/pdbsum/4o7c PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4o7c ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Disease == | == Disease == | ||
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
</div> | </div> | ||
<div class="pdbe-citations 4o7c" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Bromodomain-containing protein|Bromodomain-containing protein]] | |||
== References == | == References == | ||
<references/> | <references/> | ||
Revision as of 13:48, 11 August 2016
Crystal structure of the first bromodomain of human BRD4 in complex with SB-614067-RCrystal structure of the first bromodomain of human BRD4 in complex with SB-614067-R
Structural highlights
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.[1] [2] Function[BRD4_HUMAN] Plays a role in a process governing chromosomal dynamics during mitosis (By similarity). Publication Abstract from PubMedMembers of the bromodomain and extra terminal (BET) family of proteins are essential for the recognition of acetylated lysine (KAc) residues in histones and have emerged as promising drug targets in cancer, inflammation, and contraception research. In co-crystallization screening campaigns using the first bromodomain of BRD4 (BRD4-1) against kinase inhibitor libraries, we identified and characterized 14 kinase inhibitors (10 distinct chemical scaffolds) as ligands of the KAc binding site. Among these, the PLK1 inhibitor BI2536 and the JAK2 inhibitor TG101209 displayed strongest inhibitory potential against BRD4 (IC50 = 25 nM and 130 nM, respectively) and high selectivity for BET bromodomains. Comparative structural analysis revealed markedly different binding modes of kinase hinge-binding scaffolds in the KAc binding site, suggesting that BET proteins are potential off-targets of diverse kinase inhibitors. Combined, these findings provide a new structural framework for the rational design of next-generation BET-selective and dual-activity BET-kinase inhibitors. Acetyl-lysine Binding Site of Bromodomain-Containing Protein 4 (BRD4) Interacts with Diverse Kinase Inhibitors.,Ember SW, Zhu JY, Olesen SH, Martin MP, Becker A, Berndt N, Georg GI, Schonbrunn E ACS Chem Biol. 2014 Mar 13. PMID:24568369[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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