4yh4

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==Crystal structure of human BRD4(1) in complex with 4-[(5-phenylpyridin-3-yl)carbonyl]-3,4-dihydroquinoxalin-2(1H)-one (compound 19d)==
==Crystal structure of human BRD4(1) in complex with 4-[(5-phenylpyridin-3-yl)carbonyl]-3,4-dihydroquinoxalin-2(1H)-one (compound 19d)==
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<StructureSection load='4yh4' size='340' side='right' caption='[[4yh4]], [[Resolution|resolution]] 1.33&Aring;' scene=''>
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<StructureSection load='4yh4' size='340' side='right'caption='[[4yh4]], [[Resolution|resolution]] 1.33&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[4yh4]] 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=4YH4 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4YH4 FirstGlance]. <br>
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<table><tr><td colspan='2'>[[4yh4]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4YH4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4YH4 FirstGlance]. <br>
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=Y81:4-[(5-PHENYLPYRIDIN-3-YL)CARBONYL]-3,4-DIHYDROQUINOXALIN-2(1H)-ONE'>Y81</scene></td></tr>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.33&#8491;</td></tr>
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<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4yh3|4yh3]]</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=Y81:4-[(5-PHENYLPYRIDIN-3-YL)CARBONYL]-3,4-DIHYDROQUINOXALIN-2(1H)-ONE'>Y81</scene></td></tr>
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<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>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4yh4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4yh4 OCA], [https://pdbe.org/4yh4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4yh4 RCSB], [https://www.ebi.ac.uk/pdbsum/4yh4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4yh4 ProSAT]</span></td></tr>
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<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=4yh4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4yh4 OCA], [http://pdbe.org/4yh4 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4yh4 RCSB], [http://www.ebi.ac.uk/pdbsum/4yh4 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4yh4 ProSAT]</span></td></tr>
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</table>
</table>
== Disease ==
== Disease ==
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[[http://www.uniprot.org/uniprot/BRD4_HUMAN 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.<ref>PMID:12543779</ref> <ref>PMID:11733348</ref>
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[https://www.uniprot.org/uniprot/BRD4_HUMAN 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.<ref>PMID:12543779</ref> <ref>PMID:11733348</ref>
== Function ==
== Function ==
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[[http://www.uniprot.org/uniprot/BRD4_HUMAN BRD4_HUMAN]] Plays a role in a process governing chromosomal dynamics during mitosis (By similarity).
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[https://www.uniprot.org/uniprot/BRD4_HUMAN BRD4_HUMAN] Plays a role in a process governing chromosomal dynamics during mitosis (By similarity).
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Bromodomains are key transcriptional regulators that are thought to be druggable epigenetic targets for cancer, inflammation, diabetes and cardiovascular therapeutics. Of particular importance is the first of two bromodomains in bromodomain containing 4 protein (BRD4(1)). Protein-ligand docking in BRD4(1) was used to purchase a small, focused screening set of compounds possessing a large variety of core structures. Within this set, a small number of weak hits each contained a dihydroquinoxalinone ring system. We purchased other analogs with this ring system and further validated the new hit series and obtained improvement in binding inhibition. Limited exploration by new analog synthesis showed that the binding inhibition in a FRET assay could be improved to the low muM level making this new core a potential hit-to-lead series. Additionally, the predicted geometries of the initial hit and an improved analog were confirmed by X-ray co-crystallography with BRD4(1).
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Discovery of a new chemical series of BRD4(1) inhibitors using protein-ligand docking and structure-guided design.,Duffy BC, Liu S, Martin GS, Wang R, Hsia MM, Zhao H, Guo C, Ellis M, Quinn JF, Kharenko OA, Norek K, Gesner EM, Young PR, McLure KG, Wagner GS, Lakshminarasimhan D, White A, Suto RK, Hansen HC, Kitchen DB Bioorg Med Chem Lett. 2015 Jul 15;25(14):2818-23. doi:, 10.1016/j.bmcl.2015.04.107. Epub 2015 May 11. PMID:26022843<ref>PMID:26022843</ref>
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==See Also==
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*[[Bromodomain-containing protein 3D structures|Bromodomain-containing protein 3D structures]]
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 4yh4" style="background-color:#fffaf0;"></div>
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== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
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[[Category: Human]]
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[[Category: Homo sapiens]]
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[[Category: Lakshminarasimhan, D]]
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[[Category: Large Structures]]
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[[Category: Suto, R K]]
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[[Category: Lakshminarasimhan D]]
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[[Category: White, A]]
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[[Category: Suto RK]]
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[[Category: Protein binding]]
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[[Category: White A]]

Current revision

Crystal structure of human BRD4(1) in complex with 4-[(5-phenylpyridin-3-yl)carbonyl]-3,4-dihydroquinoxalin-2(1H)-one (compound 19d)

PDB ID 4yh4

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