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4hxp

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==Brd4 Bromodomain 1 complex with 4-(2-OXO-1,3-OXAZOLIDIN-3-YL)BENZAMIDE inhibitor==
==Brd4 Bromodomain 1 complex with 4-(2-OXO-1,3-OXAZOLIDIN-3-YL)BENZAMIDE inhibitor==
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<StructureSection load='4hxp' size='340' side='right' caption='[[4hxp]], [[Resolution|resolution]] 1.73&Aring;' scene=''>
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<StructureSection load='4hxp' size='340' side='right'caption='[[4hxp]], [[Resolution|resolution]] 1.73&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[4hxp]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4HXP OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4HXP FirstGlance]. <br>
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<table><tr><td colspan='2'>[[4hxp]] 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=4HXP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4HXP 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=1A5:4-(2-OXO-1,3-OXAZOLIDIN-3-YL)BENZAMIDE'>1A5</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]] 1.73&#8491;</td></tr>
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<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4hxk|4hxk]], [[4hxl|4hxl]], [[4hxm|4hxm]], [[4hxn|4hxn]], [[4hxo|4hxo]], [[4hxr|4hxr]], [[4hxs|4hxs]]</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=1A5:4-(2-OXO-1,3-OXAZOLIDIN-3-YL)BENZAMIDE'>1A5</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 Homo sapiens])</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=4hxp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4hxp OCA], [https://pdbe.org/4hxp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4hxp RCSB], [https://www.ebi.ac.uk/pdbsum/4hxp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4hxp 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=4hxp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4hxp OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4hxp RCSB], [http://www.ebi.ac.uk/pdbsum/4hxp PDBsum]</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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Recognizing acetyllysine of histone is a vital process of epigenetic regulations, which is mediated by a protein module called bromodomain. To contribute novel scaffolds for developing into bromodomain inhibitors, we utilize a fragment-based drug discovery approach. By successively applying docking and X-ray crystallography, we were able to identify 9 fragment hits from diffracting more than 60 crystals. In the present work, we described four of them, and carried out the integrated lead optimization for fragment 8, which bears a 2-thiazolidinone core. After several rounds of structure guided modifications, we assessed the druggability of 2-thiazolidinone by modulating in vitro pharmacokinetic studies and cellular activity assay. The results showed that two potent compounds of 2-thiazolidinones have good metabolic stability. Also the cellular assay confirmed the activities of 2-thiazolidinones. Together, we hope the identified 2-thiazolidinone chemotype as well as other fragment hits described herein, can stimulate researchers to develop more diversified bromodomain inhibitors.
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Fragment-based Drug Discovery of 2-thiazolidinones as Inhibitors of the Histone Reader BRD4 Bromodomain.,Zhao L, Cao D, Chen T, Wang Y, Miao ZH, Xu Y, Chen W, Wang X, Li Y, Du Z, Xiong B, Li J, Xu C, Zhang N, He J, Shen J J Med Chem. 2013 Mar 26. PMID:23530754<ref>PMID:23530754</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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==See Also==
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</div>
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*[[Bromodomain-containing protein 3D structures|Bromodomain-containing protein 3D structures]]
== References ==
== References ==
<references/>
<references/>
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</StructureSection>
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Cao, D Y]]
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[[Category: Large Structures]]
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[[Category: Chen, T T]]
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[[Category: Cao DY]]
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[[Category: Chen, W Y]]
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[[Category: Chen TT]]
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[[Category: Shen, J K]]
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[[Category: Chen WY]]
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[[Category: Xiong, B]]
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[[Category: Shen JK]]
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[[Category: Xu, Y C]]
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[[Category: Xiong B]]
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[[Category: Brd4]]
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[[Category: Xu YC]]
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[[Category: Bromodomain]]
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[[Category: Four alpha helice]]
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[[Category: Protein binding-inhibitor complex]]
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Current revision

Brd4 Bromodomain 1 complex with 4-(2-OXO-1,3-OXAZOLIDIN-3-YL)BENZAMIDE inhibitor

PDB ID 4hxp

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