6hdq
From Proteopedia
(Difference between revisions)
(New page: '''Unreleased structure''' The entry 6hdq is ON HOLD Authors: Chung, C. Description: N-TERMINAL BROMODOMAIN OF HUMAN BRD4 WITH : 8-(((1R,2R,3R,5S)-2-(2-(4,4-difluorocyclohexyl)ethyl)-8...) |
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| - | '''Unreleased structure''' | ||
| - | + | ==N-TERMINAL BROMODOMAIN OF HUMAN BRD4 WITH : 8-(((1R,2R,3R,5S)-2-(2-(4,4-difluorocyclohexyl)ethyl)-8-azabicyclo[3.2.1]octan-3-yl)amino)-3-methyl-5-(5-methylpyridin-3-yl)-1,7-naphthyridin-2(1H)-one== | |
| + | <StructureSection load='6hdq' size='340' side='right' caption='[[6hdq]], [[Resolution|resolution]] 1.70Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[6hdq]] is a 1 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=6HDQ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6HDQ FirstGlance]. <br> | ||
| + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=FZE:8-(((1R,2R,3R,5S)-2-(2-(4,4-difluorocyclohexyl)ethyl)-8-azabicyclo[3.2.1]octan-3-yl)amino)-3-methyl-5-(5-methylpyridin-3-yl)-1,7-naphthyridin-2(1H)-one'>FZE</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=6hdq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6hdq OCA], [http://pdbe.org/6hdq PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6hdq RCSB], [http://www.ebi.ac.uk/pdbsum/6hdq PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6hdq ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Disease == | ||
| + | [[http://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 == | ||
| + | [[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 == | ||
| + | ATAD2 is a cancer-associated protein whose bromodomain has been described as among the least druggable of its class. In our recent disclosure of the first chemical probe against this bromodomain, GSK8814 (6), we described the use of a conformationally constrained methoxy piperidine to gain selectivity over the BET bromodomains. Here we describe an orthogonal conformational restriction strategy of the piperidine ring to give potent and selective tropane inhibitors and show structural insights into why this was more challenging than expected. Greater understanding of why different rational approaches succeeded or failed should help in the future design of selectivity in the bromodomain family. | ||
| - | + | Aiming to Miss a Moving Target: Bromo and Extra Terminal Domain (BET) Selectivity in Constrained ATAD2 Inhibitors.,Bamborough P, Chung CW, Furze RC, Grandi P, Michon AM, Watson RJ, Mitchell DJ, Barnett H, Prinjha RK, Rau C, Sheppard RJ, Werner T, Demont EH J Med Chem. 2018 Sep 18. doi: 10.1021/acs.jmedchem.8b00862. PMID:30226378<ref>PMID:30226378</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| + | <div class="pdbe-citations 6hdq" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Human]] | ||
[[Category: Chung, C]] | [[Category: Chung, C]] | ||
| + | [[Category: Antagonist]] | ||
| + | [[Category: Brd4]] | ||
| + | [[Category: Bromodomain]] | ||
| + | [[Category: Bromodomain containing protein 4]] | ||
| + | [[Category: Epigenetic reader]] | ||
| + | [[Category: Histone]] | ||
| + | [[Category: Inhibitor]] | ||
| + | [[Category: Transcription]] | ||
Current revision
N-TERMINAL BROMODOMAIN OF HUMAN BRD4 WITH : 8-(((1R,2R,3R,5S)-2-(2-(4,4-difluorocyclohexyl)ethyl)-8-azabicyclo[3.2.1]octan-3-yl)amino)-3-methyl-5-(5-methylpyridin-3-yl)-1,7-naphthyridin-2(1H)-one
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