6k04
From Proteopedia
(Difference between revisions)
(New page: '''Unreleased structure''' The entry 6k04 is ON HOLD Authors: Lu, T., Lu, W., Chen, D., Zhao, Y., Luo, C. Description: Crystal structure of BRD2(BD2)with ligand BY27 bound [[Category: ...) |
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| - | '''Unreleased structure''' | ||
| - | + | ==Crystal structure of BRD2(BD2)with ligand BY27 bound== | |
| + | <StructureSection load='6k04' size='340' side='right'caption='[[6k04]], [[Resolution|resolution]] 1.25Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[6k04]] 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=6K04 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6K04 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]] 1.251Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CQF:(6~{R})-~{N}-(4-chlorophenyl)-1-methyl-8-(1-methylpyrazol-4-yl)-5,6-dihydro-4~{H}-[1,2,4]triazolo[4,3-a][1]benzazepin-6-amine'>CQF</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=6k04 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6k04 OCA], [https://pdbe.org/6k04 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6k04 RCSB], [https://www.ebi.ac.uk/pdbsum/6k04 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6k04 ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/BRD2_HUMAN BRD2_HUMAN] May play a role in spermatogenesis or folliculogenesis (By similarity). Binds hyperacetylated chromatin and plays a role in the regulation of transcription, probably by chromatin remodeling. Regulates transcription of the CCND1 gene. Plays a role in nucleosome assembly.<ref>PMID:18406326</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Recently, selective inhibition of BET BD2 is emerging as a promising strategy for drug discovery. Despite significant progress in this area, systematic studies of selective BET BD2 inhibitors are still few. In this study, we report the discovery of a potent and selective BET BD2 inhibitor BY27 (47). Our high resolution co-crystal structures of 47/BRD2 BD1 and BD2 showed that the triazole group of 47, water molecules, H433 and N429 in BRD2 BD2 established a water-bridged H-bonding network, which is responsible for the observed selectivities. DNA microarray analysis of HepG2 cells treated with 47 or OTX015 demonstrated the transcriptome impact differences between a BET BD2 selective inhibitor and a pan BET inhibitor. In a MV4-11 mouse xenograft model, 47 caused 67% of tumor growth inhibition and was less toxic than a pan BET inhibitor 1â¯at high doses. We conclude that the improved safety profile of selective BET BD2 inhibitors warrant future studies in BET associated diseases. | ||
| - | + | Discovery, structural insight, and bioactivities of BY27 as a selective inhibitor of the second bromodomains of BET proteins.,Chen D, Lu T, Yan Z, Lu W, Zhou F, Lyu X, Xu B, Jiang H, Chen K, Luo C, Zhao Y Eur J Med Chem. 2019 Nov 15;182:111633. doi: 10.1016/j.ejmech.2019.111633. Epub , 2019 Aug 21. PMID:31461688<ref>PMID:31461688</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| - | [[Category: Chen | + | <div class="pdbe-citations 6k04" style="background-color:#fffaf0;"></div> |
| - | [[Category: Lu | + | |
| - | [[Category: | + | ==See Also== |
| - | [[Category: | + | *[[Bromodomain-containing protein 3D structures|Bromodomain-containing protein 3D structures]] |
| - | [[Category: Zhao | + | == References == |
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Chen D]] | ||
| + | [[Category: Lu T]] | ||
| + | [[Category: Lu W]] | ||
| + | [[Category: Luo C]] | ||
| + | [[Category: Zhao Y]] | ||
Current revision
Crystal structure of BRD2(BD2)with ligand BY27 bound
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Categories: Homo sapiens | Large Structures | Chen D | Lu T | Lu W | Luo C | Zhao Y
