This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.
Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.
6k04
From Proteopedia
(Difference between revisions)
| Line 1: | Line 1: | ||
| - | '''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: | + | <div class="pdbe-citations 6k04" style="background-color:#fffaf0;"></div> |
| - | [[Category: | + | |
| - | [[Category: | + | ==See Also== |
| - | [[Category: | + | *[[Bromodomain-containing protein 3D structures|Bromodomain-containing protein 3D structures]] |
| - | [[Category: | + | == 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
| |||||||||||
Categories: Homo sapiens | Large Structures | Chen D | Lu T | Lu W | Luo C | Zhao Y
