View source for 4bw3


==The first bromodomain of human BRD4 in complex with 3,5 dimethylisoxaxole ligand==
<StructureSection load='4bw3' size='340' side='right'caption='[[4bw3]], [[Resolution|resolution]] 1.50&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4bw3]] 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=4BW3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4BW3 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]] 1.5&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=9BM:4-((2-(TERT-BUTYL)PHENYL)AMINO)-7-(3,5-DIMETHYLISOXAZOL-4-YL)-6-METHOXY-1,5-NAPHTHYRIDINE-3-CARBOXYLIC+ACID'>9BM</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</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=4bw3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4bw3 OCA], [https://pdbe.org/4bw3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4bw3 RCSB], [https://www.ebi.ac.uk/pdbsum/4bw3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4bw3 ProSAT]</span></td></tr>
</table>
== Disease ==
[https://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 ==
[https://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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== Publication Abstract from PubMed ==
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.

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>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4bw3" style="background-color:#fffaf0;"></div>

==See Also==
*[[Bromodomain-containing protein 3D structures|Bromodomain-containing protein 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Bamborough P]]
[[Category: Bouillot A]]
[[Category: Chung C]]
[[Category: Delannee D]]
[[Category: Dudit Y]]
[[Category: Gellibert F]]
[[Category: Huet P]]
[[Category: Krysa G]]
[[Category: Lamotte Y]]
[[Category: Lewis A]]
[[Category: Mirguet O]]
[[Category: Nicodeme E]]
[[Category: Trottet L]]
[[Category: Witherington J]]