7dn4
From Proteopedia
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| - | '''Unreleased structure''' | ||
| - | The | + | ==The crystal structure of Cpd8 in complex with BPTF bromodomain== |
| + | <StructureSection load='7dn4' size='340' side='right'caption='[[7dn4]], [[Resolution|resolution]] 2.84Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[7dn4]] is a 6 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=7DN4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7DN4 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]] 2.841Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=JC3:3-methyl-2-[[(3R,5R)-1-methyl-5-phenyl-piperidin-3-yl]amino]-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-one'>JC3</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=7dn4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7dn4 OCA], [https://pdbe.org/7dn4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7dn4 RCSB], [https://www.ebi.ac.uk/pdbsum/7dn4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7dn4 ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/BPTF_HUMAN BPTF_HUMAN] Histone-binding component of NURF (nucleosome-remodeling factor), a complex which catalyzes ATP-dependent nucleosome sliding and facilitates transcription of chromatin. Specifically recognizes H3 tails trimethylated on 'Lys-4' (H3K4me3), which mark transcription start sites of virtually all active genes. May also regulate transcription through direct binding to DNA or transcription factors. | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Bromodomain and PHD finger containing transcription factor (BPTF) is a multidomain protein that regulates the transcription of chromatin and is related to many cancers. Herein, we report the screening-based discovery of Cpd1, a compound with micromolar affinity to the BPTF bromodomain. Through structure-guided optimization, we synthesized a variety of new inhibitors. Among these compounds, Cpd8 and Cpd10 were highly potent and selective inhibitors, with KD values of 428 nM and 655 nM in ITC assays, respectively. The high activity was explained by the cocrystal structure of Cpd8 in complex with the BPTF bromodomain protein. Cpd8 and Cpd10 were able to stabilize the BPTF bromodomain protein in cells in a cellular thermal shift assay (CETSA). Cpd8 downregulated c-MYC expression in A549 cells. All experiments prove that these two compounds are potential BPTF inhibitors. | ||
| - | + | Discovery of selective BPTF bromodomain inhibitors by screening and structure-based optimization.,Xiong L, Mao X, Guo Y, Zhou Y, Chen M, Chen P, Yang S, Li L Biochem Biophys Res Commun. 2021 Mar 19;545:125-131. doi:, 10.1016/j.bbrc.2021.01.067. Epub 2021 Feb 3. PMID:33548625<ref>PMID:33548625</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| + | <div class="pdbe-citations 7dn4" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Guo Y]] | ||
| + | [[Category: Xiong L]] | ||
| + | [[Category: Yang S]] | ||
Current revision
The crystal structure of Cpd8 in complex with BPTF bromodomain
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Categories: Homo sapiens | Large Structures | Guo Y | Xiong L | Yang S
