4qb3: Difference between revisions
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==Crystal structure of the first bromodomain of human BRD4 in complex with Olinone== | ==Crystal structure of the first bromodomain of human BRD4 in complex with Olinone== | ||
<StructureSection load='4qb3' size='340' side='right' caption='[[4qb3]], [[Resolution|resolution]] 0.94Å' scene=''> | <StructureSection load='4qb3' size='340' side='right'caption='[[4qb3]], [[Resolution|resolution]] 0.94Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4qb3]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4QB3 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4QB3 FirstGlance]. <br> | <table><tr><td colspan='2'>[[4qb3]] 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=4QB3 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4QB3 FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=30M:N-[4-(1-OXO-1,2,3,4-TETRAHYDRO-5H-PYRIDO[4,3-B]INDOL-5-YL)BUTYL]ACETAMIDE'>30M</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=30M:N-[4-(1-OXO-1,2,3,4-TETRAHYDRO-5H-PYRIDO[4,3-B]INDOL-5-YL)BUTYL]ACETAMIDE'>30M</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene></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=4qb3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4qb3 OCA], [http://pdbe.org/4qb3 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4qb3 RCSB], [http://www.ebi.ac.uk/pdbsum/4qb3 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4qb3 ProSAT]</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=4qb3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4qb3 OCA], [http://pdbe.org/4qb3 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4qb3 RCSB], [http://www.ebi.ac.uk/pdbsum/4qb3 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4qb3 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
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</div> | </div> | ||
<div class="pdbe-citations 4qb3" style="background-color:#fffaf0;"></div> | <div class="pdbe-citations 4qb3" style="background-color:#fffaf0;"></div> | ||
==See Also== | |||
*[[Bromodomain-containing protein 3D structures|Bromodomain-containing protein 3D structures]] | |||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Human]] | |||
[[Category: Large Structures]] | |||
[[Category: Joshua, J]] | [[Category: Joshua, J]] | ||
[[Category: Plotnikov, A N]] | [[Category: Plotnikov, A N]] | ||
Revision as of 11:39, 24 April 2019
Crystal structure of the first bromodomain of human BRD4 in complex with OlinoneCrystal structure of the first bromodomain of human BRD4 in complex with Olinone
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 PubMedLysine 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[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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