4qr4

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==Brd4 Bromodomain 1 complex with its novel inhibitors==
==Brd4 Bromodomain 1 complex with its novel inhibitors==
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<StructureSection load='4qr4' size='340' side='right' caption='[[4qr4]], [[Resolution|resolution]] 1.28&Aring;' scene=''>
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<StructureSection load='4qr4' size='340' side='right'caption='[[4qr4]], [[Resolution|resolution]] 1.28&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[4qr4]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4QR4 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4QR4 FirstGlance]. <br>
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<table><tr><td colspan='2'>[[4qr4]] 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=4QR4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4QR4 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=BNK:2-CHLORO-N-CYCLOPENTYL-5-(2-OXO-2,3-DIHYDRO-1,3-THIAZOL-4-YL)BENZENESULFONAMIDE'>BNK</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]] 1.28&#8491;</td></tr>
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<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4qr3|4qr3]], [[4qr5|4qr5]]</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=BNK:2-CHLORO-N-CYCLOPENTYL-5-(2-OXO-2,3-DIHYDRO-1,3-THIAZOL-4-YL)BENZENESULFONAMIDE'>BNK</scene></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=4qr4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4qr4 OCA], [http://pdbe.org/4qr4 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4qr4 RCSB], [http://www.ebi.ac.uk/pdbsum/4qr4 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4qr4 ProSAT]</span></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=4qr4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4qr4 OCA], [https://pdbe.org/4qr4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4qr4 RCSB], [https://www.ebi.ac.uk/pdbsum/4qr4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4qr4 ProSAT]</span></td></tr>
</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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The signal transduction of acetylated histone can be processed through a recognition module, bromodomain. Several inhibitors targeting BRD4, one of the bromodomain members, are in clinical trials as anticancer drugs. Hereby, we report our efforts on discovery and optimization of a new series of 2-thiazolidinones as BRD4 inhibitors along our previous study. In this work, guided by crystal structure analysis, we reversed the sulfonamide group and identified a new binding mode. A structure-activity relationship study on this new series led to several potent BRD4 inhibitors with IC50 of about 0.05-0.1 muM in FP binding assay and GI50 of 0.1-0.3 muM in cell based assays. To complete the lead-like assessment of this series, we further checked its effects on BRD4 downstream protein c-Myc, investigated its selectivity among five different bromodomain proteins, as well as the metabolic stability test, and reinforced the utility of 2-thiazolidinone scaffold as BET bromodomain inhibitors in novel anticancer drug development.
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Fragment-based drug discovery of 2-thiazolidinones as BRD4 inhibitors: 2. Structure-based optimization.,Zhao L, Wang Y, Cao D, Chen T, Wang Q, Li Y, Xu Y, Zhang N, Wang X, Chen D, Chen L, Chen YL, Xia G, Shi Z, Liu YC, Lin Y, Miao Z, Shen J, Xiong B J Med Chem. 2015 Feb 12;58(3):1281-97. doi: 10.1021/jm501504k. Epub 2015 Jan 14. PMID:25559428<ref>PMID:25559428</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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</div>
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<div class="pdbe-citations 4qr4" style="background-color:#fffaf0;"></div>
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==See Also==
==See Also==
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*[[Bromodomain-containing protein|Bromodomain-containing protein]]
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*[[Bromodomain-containing protein 3D structures|Bromodomain-containing protein 3D structures]]
== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
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[[Category: Cao, D Y]]
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[[Category: Homo sapiens]]
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[[Category: Chen, T T]]
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[[Category: Large Structures]]
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[[Category: Xiong, B]]
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[[Category: Cao DY]]
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[[Category: Xu, Y C]]
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[[Category: Chen TT]]
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[[Category: Brd4]]
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[[Category: Xiong B]]
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[[Category: Bromodomain]]
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[[Category: Xu YC]]
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[[Category: Four alpha helice]]
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[[Category: Transcription-transcription inhibitor complex]]
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Current revision

Brd4 Bromodomain 1 complex with its novel inhibitors

PDB ID 4qr4

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