6djc
From Proteopedia
(Difference between revisions)
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<StructureSection load='6djc' size='340' side='right' caption='[[6djc]], [[Resolution|resolution]] 1.46Å' scene=''> | <StructureSection load='6djc' size='340' side='right' caption='[[6djc]], [[Resolution|resolution]] 1.46Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>[[6djc]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6DJC OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6DJC FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6djc]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6DJC OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6DJC FirstGlance]. <br> |
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CF6:N,N-(decane-1,10-diyl)bis{2-[(6S)-4-(4-chlorophenyl)-2,3,9-trimethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin-6-yl]acetamide}'>CF6</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CF6:N,N-(decane-1,10-diyl)bis{2-[(6S)-4-(4-chlorophenyl)-2,3,9-trimethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin-6-yl]acetamide}'>CF6</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene></td></tr> | ||
| + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">BRD4, HUNK1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | ||
<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=6djc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6djc OCA], [http://pdbe.org/6djc PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6djc RCSB], [http://www.ebi.ac.uk/pdbsum/6djc PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6djc ProSAT]</span></td></tr> | <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=6djc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6djc OCA], [http://pdbe.org/6djc PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6djc RCSB], [http://www.ebi.ac.uk/pdbsum/6djc PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6djc ProSAT]</span></td></tr> | ||
</table> | </table> | ||
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== Function == | == Function == | ||
[[http://www.uniprot.org/uniprot/BRD4_HUMAN BRD4_HUMAN]] Plays a role in a process governing chromosomal dynamics during mitosis (By similarity). | [[http://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 == | ||
| + | The importance of BET protein BRD4 in gene transcription is well recognized through the study of chemical modulation of its characteristic tandem bromodomain (BrD) binding to lysine-acetylated histones and transcription factors. However, while monovalent inhibition of BRD4 by BET BrD inhibitors such as JQ1 blocks growth of hematopoietic cancers, it is much less effective generally in solid tumors. Here, we report a thienodiazepine-based bivalent BrD inhibitor, MS645, that affords spatially constrained tandem BrD inhibition and consequently sustained repression of BRD4 transcriptional activity in blocking proliferation of solid-tumor cells including a panel of triple-negative breast cancer (TNBC) cells. MS645 blocks BRD4 binding to transcription enhancer/mediator proteins MED1 and YY1 with potency superior to monovalent BET inhibitors, resulting in down-regulation of proinflammatory cytokines and genes for cell-cycle control and DNA damage repair that are largely unaffected by monovalent BrD inhibition. Our study suggests a therapeutic strategy to maximally control BRD4 activity for rapid growth of solid-tumor TNBC cells. | ||
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| + | Spatially constrained tandem bromodomain inhibition bolsters sustained repression of BRD4 transcriptional activity for TNBC cell growth.,Ren C, Zhang G, Han F, Fu S, Cao Y, Zhang F, Zhang Q, Meslamani J, Xu Y, Ji D, Cao L, Zhou Q, Cheung KL, Sharma R, Babault N, Yi Z, Zhang W, Walsh MJ, Zeng L, Zhou MM Proc Natl Acad Sci U S A. 2018 Jul 16. pii: 1720000115. doi:, 10.1073/pnas.1720000115. PMID:30012592<ref>PMID:30012592</ref> | ||
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| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 6djc" style="background-color:#fffaf0;"></div> | ||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| + | [[Category: Human]] | ||
[[Category: Ren, C]] | [[Category: Ren, C]] | ||
[[Category: Zhou, M M]] | [[Category: Zhou, M M]] | ||
Revision as of 19:08, 1 August 2018
Crystal structure of human Bromodomain-containing protein 4 (BRD4) bromodomain with MS645
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