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4bw2

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Revision as of 12:53, 11 August 2016

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

Structural highlights

4bw2 is a 1 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
Related:	4bw1, 4bw3, 4bw4
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[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.^[1] ^[2]

Function

[BRD4_HUMAN] Plays a role in a process governing chromosomal dynamics during mitosis (By similarity).

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^[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ French CA, Miyoshi I, Kubonishi I, Grier HE, Perez-Atayde AR, Fletcher JA. BRD4-NUT fusion oncogene: a novel mechanism in aggressive carcinoma. Cancer Res. 2003 Jan 15;63(2):304-7. PMID:12543779
↑ French CA, Miyoshi I, Aster JC, Kubonishi I, Kroll TG, Dal Cin P, Vargas SO, Perez-Atayde AR, Fletcher JA. BRD4 bromodomain gene rearrangement in aggressive carcinoma with translocation t(15;19). Am J Pathol. 2001 Dec;159(6):1987-92. PMID:11733348 doi:10.1016/S0002-9440(10)63049-0
↑ 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. Naphthyridines as Novel BET Family Bromodomain Inhibitors. ChemMedChem. 2013 Sep 2. doi: 10.1002/cmdc.201300259. PMID:24000170 doi:10.1002/cmdc.201300259

1 Structural highlights
2 Disease
3 Function
4 Publication Abstract from PubMed
5 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4bw2"

@@ Line 1: / Line 1: @@
 ==The first bromodomain of human BRD4 in complex with 3,5 dimethylisoxaxole ligand==
 <StructureSection load='4bw2' size='340' side='right' caption='[[4bw2]], [[Resolution|resolution]] 1.92&Aring;' scene=''>
@@ Line 5: / Line 6: @@
 </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>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4bw1|4bw1]], [[4bw3|4bw3]], [[4bw4|4bw4]]</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=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>
+<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://pdbe.org/4bw2 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4bw2 RCSB], [http://www.ebi.ac.uk/pdbsum/4bw2 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4bw2 ProSAT]</span></td></tr>
 </table>
 == Disease ==
@@ Line 19: / Line 20: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 4bw2" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Bromodomain-containing protein|Bromodomain-containing protein]]
 == References ==
 <references/>

4bw2

From Proteopedia

Revision as of 12:53, 11 August 2016

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

Structural highlights

Disease

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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