5wuu: Difference between revisions

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New page: '''Unreleased structure''' The entry 5wuu is ON HOLD Authors: Zhang, H., Sun, Z.Y. Description: complex structure of the first bromodomain of BRD4 with an inhibitor that containing a 2...
 
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'''Unreleased structure'''


The entry 5wuu is ON HOLD
==Complex structure of the first bromodomain of BRD4 with an inhibitor that containing a 2H-chromen-2-one ring==
<StructureSection load='5wuu' size='340' side='right'caption='[[5wuu]], [[Resolution|resolution]] 1.72&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5wuu]] 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=5WUU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5WUU FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.724&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=7UU:~{N}-METHYL-~{N}-[3-[(2-OXIDANYLIDENECHROMEN-4-YL)AMINO]PROPYL]THIOPHENE-2-CARBOXAMIDE'>7UU</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5wuu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5wuu OCA], [https://pdbe.org/5wuu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5wuu RCSB], [https://www.ebi.ac.uk/pdbsum/5wuu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5wuu ProSAT]</span></td></tr>
</table>
== Disease ==
[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 ==
[https://www.uniprot.org/uniprot/BRD4_HUMAN BRD4_HUMAN] Plays a role in a process governing chromosomal dynamics during mitosis (By similarity).
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
As an epigenetic reader, BRD4 regulates the transcription of important downstream genes that are essential for the survival of tumor cells. Small molecular inhibitors targeting the first bromodomain of BRD4 (BRD4-BD1) have showed promising potentials in the therapies of BRD4-related cancers. Through AlphaScreen-based high-throughput screening assay, a novel small molecular inhibitor was identified, and named DCBD-005, which inhibited the binding between BRD4-BD1 and acetylated lysines with an IC50 value of 0.81+/-0.03muM. The compound DCBD-005 effectively inhibited the viability, caused cell cycle arrest, and induced apoptosis in human leukemia MV4-11 cells. Moreover, the crystal structure of compound DCBD-005 with the BRD4-BD1 was determined at 1.72A resolution, which revealed the binding mechanism of the leading compound, and also provided solid basis for further structure-based optimization. These results indicated that this novel BRD4-BD1 inhibitor DCBD-005 is promising to be developed into a drug candidate in the treatment of BRD4-related diseases.


Authors: Zhang, H., Sun, Z.Y.
Discovery of novel BRD4 inhibitors by high-throughput screening, crystallography, and cell-based assays.,Sun Z, Zhang H, Chen Z, Xie Y, Jiang H, Chen L, Ding H, Zhang Y, Jiang H, Zheng M, Luo C Bioorg Med Chem Lett. 2017 May 1;27(9):2003-2009. doi:, 10.1016/j.bmcl.2017.03.012. Epub 2017 Mar 9. PMID:28347667<ref>PMID:28347667</ref>


Description: complex structure of the first bromodomain of BRD4 with an inhibitor that containing a 2H-chromen-2-one ring
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
[[Category: Unreleased Structures]]
</div>
[[Category: Zhang, H]]
<div class="pdbe-citations 5wuu" style="background-color:#fffaf0;"></div>
[[Category: Sun, Z.Y]]
 
==See Also==
*[[Bromodomain-containing protein 3D structures|Bromodomain-containing protein 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Sun ZY]]
[[Category: Zhang H]]
Retrieved from "https://proteopedia.org/5wuu"