4hxr

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==Brd4 Bromodomain 1 complex with N-[3-(2-OXO-2,3-DIHYDRO-1,3-THIAZOL-4-YL)PHENYL]THIOPHENE-2-SULFONAMIDE inhibitor==
==Brd4 Bromodomain 1 complex with N-[3-(2-OXO-2,3-DIHYDRO-1,3-THIAZOL-4-YL)PHENYL]THIOPHENE-2-SULFONAMIDE inhibitor==
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<StructureSection load='4hxr' size='340' side='right' caption='[[4hxr]], [[Resolution|resolution]] 1.53&Aring;' scene=''>
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<StructureSection load='4hxr' size='340' side='right'caption='[[4hxr]], [[Resolution|resolution]] 1.53&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[4hxr]] 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=4HXR OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4HXR FirstGlance]. <br>
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<table><tr><td colspan='2'>[[4hxr]] 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=4HXR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4HXR 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=1A4:N-[3-(2-OXO-2,3-DIHYDRO-1,3-THIAZOL-4-YL)PHENYL]THIOPHENE-2-SULFONAMIDE'>1A4</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]] 1.53&#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]], [[4hxp|4hxp]], [[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=1A4:N-[3-(2-OXO-2,3-DIHYDRO-1,3-THIAZOL-4-YL)PHENYL]THIOPHENE-2-SULFONAMIDE'>1A4</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=4hxr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4hxr OCA], [https://pdbe.org/4hxr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4hxr RCSB], [https://www.ebi.ac.uk/pdbsum/4hxr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4hxr 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=4hxr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4hxr OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4hxr RCSB], [http://www.ebi.ac.uk/pdbsum/4hxr 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 N-[3-(2-OXO-2,3-DIHYDRO-1,3-THIAZOL-4-YL)PHENYL]THIOPHENE-2-SULFONAMIDE inhibitor

PDB ID 4hxr

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