4bw2

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{{STRUCTURE_4bw2| PDB=4bw2 | SCENE= }}
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==The first bromodomain of human BRD4 in complex with 3,5 dimethylisoxaxole ligand==
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===The first bromodomain of human BRD4 in complex with 3,5 dimethylisoxaxole ligand===
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<StructureSection load='4bw2' size='340' side='right' caption='[[4bw2]], [[Resolution|resolution]] 1.92&Aring;' scene=''>
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{{ABSTRACT_PUBMED_24000170}}
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== Structural highlights ==
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<table><tr><td colspan='2'>[[4bw2]] 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=4BW2 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4BW2 FirstGlance]. <br>
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==Disease==
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</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=UTH:4-((2-(TERT-BUTYL)PHENYL)AMINO)-7-(3,5-DIMETHYLISOXAZOL-4-YL)-1,8-NAPHTHYRIDINE-3-CARBOXYLIC+ACID'>UTH</scene></td></tr>
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<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4bw1|4bw1]], [[4bw3|4bw3]], [[4bw4|4bw4]]</td></tr>
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<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=4bw2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4bw2 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4bw2 RCSB], [http://www.ebi.ac.uk/pdbsum/4bw2 PDBsum]</span></td></tr>
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</table>
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== 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>
[[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>
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== Function ==
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==Function==
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[[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).
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Bromodomains (BRDs) are small protein domains found in a variety of proteins that recognize and bind to acetylated histone tails. This binding affects chromatin structure and facilitates the localisation of transcriptional complexes to specific genes, thereby regulating epigenetically controlled processes including gene transcription and mRNA elongation. Inhibitors of the bromodomain and extra-terminal (BET) proteins BRD2-4 and T, which prevent bromodomain binding to acetyl-modified histone tails, have shown therapeutic promise in several diseases. We report here the discovery of 1,5-naphthyridine derivatives as potent inhibitors of the BET bromodomain family with good cell activity and oral pharmacokinetic parameters. X-ray crystal structures of naphthyridine isomers have been solved and quantum mechanical calculations have been used to explain the higher affinity of the 1,5-isomer over the others. The best compounds were progressed in a mouse model of inflammation and exhibited dose-dependent anti-inflammatory pharmacology.
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==About this Structure==
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Naphthyridines as Novel BET Family Bromodomain Inhibitors.,Mirguet O, Lamotte Y, Chung CW, Bamborough P, Delannee D, Bouillot A, Gellibert F, Krysa G, Lewis A, Witherington J, Huet P, Dudit Y, Trottet L, Nicodeme E ChemMedChem. 2013 Sep 2. doi: 10.1002/cmdc.201300259. PMID:24000170<ref>PMID:24000170</ref>
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[[4bw2]] 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=4BW2 OCA].
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==Reference==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<ref group="xtra">PMID:024000170</ref><references group="xtra"/><references/>
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</div>
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== References ==
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<references/>
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__TOC__
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</StructureSection>
[[Category: Human]]
[[Category: Human]]
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[[Category: Bamborough, P.]]
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[[Category: Bamborough, P]]
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[[Category: Bouillot, A.]]
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[[Category: Bouillot, A]]
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[[Category: Chung, C.]]
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[[Category: Chung, C]]
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[[Category: Delannee, D.]]
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[[Category: Delannee, D]]
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[[Category: Dudit, Y.]]
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[[Category: Dudit, Y]]
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[[Category: Gellibert, F.]]
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[[Category: Gellibert, F]]
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[[Category: Huet, P.]]
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[[Category: Huet, P]]
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[[Category: Krysa, G.]]
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[[Category: Krysa, G]]
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[[Category: Lamotte, Y.]]
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[[Category: Lamotte, Y]]
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[[Category: Lewis, A.]]
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[[Category: Lewis, A]]
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[[Category: Mirguet, O.]]
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[[Category: Mirguet, O]]
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[[Category: Nicodeme, E.]]
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[[Category: Nicodeme, E]]
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[[Category: Trottet, L.]]
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[[Category: Trottet, L]]
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[[Category: Witherington, J.]]
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[[Category: Witherington, J]]
[[Category: Antagonist]]
[[Category: Antagonist]]
[[Category: Epigenetic reader]]
[[Category: Epigenetic reader]]

Revision as of 12:59, 4 January 2015

The first bromodomain of human BRD4 in complex with 3,5 dimethylisoxaxole ligand

4bw2, resolution 1.92Å

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