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5y8y

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==Crystal Structure Analysis of the BRD4==
==Crystal Structure Analysis of the BRD4==
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<StructureSection load='5y8y' size='340' side='right' caption='[[5y8y]], [[Resolution|resolution]] 1.87&Aring;' scene=''>
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<StructureSection load='5y8y' size='340' side='right'caption='[[5y8y]], [[Resolution|resolution]] 1.87&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[5y8y]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5Y8Y OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5Y8Y FirstGlance]. <br>
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<table><tr><td colspan='2'>[[5y8y]] 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=5Y8Y OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5Y8Y 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=8PX:5-bromanyl-2-methoxy-N-(6-methoxy-3-methyl-1,2-benzoxazol-5-yl)benzenesulfonamide'>8PX</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=NO3:NITRATE+ION'>NO3</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]] 1.87&#8491;</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=5y8y FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5y8y OCA], [http://pdbe.org/5y8y PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5y8y RCSB], [http://www.ebi.ac.uk/pdbsum/5y8y PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5y8y ProSAT]</span></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=8PX:5-bromanyl-2-methoxy-N-(6-methoxy-3-methyl-1,2-benzoxazol-5-yl)benzenesulfonamide'>8PX</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=NO3:NITRATE+ION'>NO3</scene></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=5y8y FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5y8y OCA], [https://pdbe.org/5y8y PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5y8y RCSB], [https://www.ebi.ac.uk/pdbsum/5y8y PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5y8y 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 bromodomain and extra-terminal (BET) family proteins have gained increasing interest as drug targets for treatment of castration-resistant prostate cancer (CRPC). Here, we describe the design, optimization, and evaluation of benzo[ d]isoxazole-containing compounds as potent BET bromodomain inhibitors. Cocrystal structures of the representative inhibitors in complex with BRD4(1) provided solid structural basis for compound optimization. The two most potent compounds, 6i (Y06036) and 7m (Y06137), bound to the BRD4(1) bromodomain with Kd values of 82 and 81 nM, respectively. They also exhibited high selectivity over other non-BET subfamily members. The compounds potently inhibited cell growth, colony formation, and the expression of AR, AR regulated genes, and MYC in prostate cancer cell lines. Compounds 6i and 7m also demonstrated therapeutic effects in a C4-2B CRPC xenograft tumor model in mice. These potent and selective BET inhibitors represent a new class of compounds for the development of potential therapeutics against CRPC.
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Structure-Based Discovery and Optimization of Benzo[ d]isoxazole Derivatives as Potent and Selective BET Inhibitors for Potential Treatment of Castration-Resistant Prostate Cancer (CRPC).,Zhang M, Zhang Y, Song M, Xue X, Wang J, Wang C, Zhang C, Li C, Xiang Q, Zou L, Wu X, Wu C, Dong B, Xue W, Zhou Y, Chen H, Wu D, Ding K, Xu Y J Med Chem. 2018 Apr 12;61(7):3037-3058. doi: 10.1021/acs.jmedchem.8b00103. Epub , 2018 Apr 3. PMID:29566488<ref>PMID:29566488</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 5y8y" style="background-color:#fffaf0;"></div>
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== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
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[[Category: Song, M]]
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[[Category: Homo sapiens]]
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[[Category: Wang, C]]
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[[Category: Large Structures]]
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[[Category: Xu, Y]]
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[[Category: Song M]]
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[[Category: Zhang, Y]]
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[[Category: Wang C]]
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[[Category: Bromodomain]]
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[[Category: Xu Y]]
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[[Category: Transcription]]
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[[Category: Zhang Y]]

Current revision

Crystal Structure Analysis of the BRD4

PDB ID 5y8y

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