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4bw2

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

Structural highlights

4bw2 is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.92Å
Ligands:	,
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 3: / Line 3: @@
 <StructureSection load='4bw2' size='340' side='right'caption='[[4bw2]], [[Resolution|resolution]] 1.92&Aring;' scene=''>
 == Structural highlights ==
-<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>
+<table><tr><td colspan='2'>[[4bw2]] 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=4BW2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4BW2 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=UTH:4-((2-(TERT-BUTYL)PHENYL)AMINO)-7-(3,5-DIMETHYLISOXAZOL-4-YL)-1,8-NAPHTHYRIDINE-3-CARBOXYLIC+ACID'>UTH</scene></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.92&#8491;</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='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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='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>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4bw2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4bw2 OCA], [https://pdbe.org/4bw2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4bw2 RCSB], [https://www.ebi.ac.uk/pdbsum/4bw2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4bw2 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>
+[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 ==
-[[http://www.uniprot.org/uniprot/BRD4_HUMAN BRD4_HUMAN]] Plays a role in a process governing chromosomal dynamics during mitosis (By similarity).
+[https://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 ==
@@ Line 23: / Line 23: @@
 ==See Also==
-*[[Bromodomain-containing protein|Bromodomain-containing protein]]
+*[[Bromodomain-containing protein 3D structures|Bromodomain-containing protein 3D structures]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
-[[Category: Human]]
+[[Category: Homo sapiens]]
 [[Category: Large Structures]]
-[[Category: Bamborough, P]]
+[[Category: Bamborough P]]
-[[Category: Bouillot, A]]
+[[Category: Bouillot A]]
-[[Category: Chung, C]]
+[[Category: Chung C]]
-[[Category: Delannee, D]]
+[[Category: Delannee D]]
-[[Category: Dudit, Y]]
+[[Category: Dudit Y]]
-[[Category: Gellibert, F]]
+[[Category: Gellibert F]]
-[[Category: Huet, P]]
+[[Category: Huet P]]
-[[Category: Krysa, G]]
+[[Category: Krysa G]]
-[[Category: Lamotte, Y]]
+[[Category: Lamotte Y]]
-[[Category: Lewis, A]]
+[[Category: Lewis A]]
-[[Category: Mirguet, O]]
+[[Category: Mirguet O]]
-[[Category: Nicodeme, E]]
+[[Category: Nicodeme E]]
-[[Category: Trottet, L]]
+[[Category: Trottet L]]
-[[Category: Witherington, J]]
+[[Category: Witherington J]]
-[[Category: Antagonist]]
-[[Category: Epigenetic reader]]
-[[Category: Histone]]
-[[Category: Inhibitor]]
-[[Category: Transcription]]

4bw2

From Proteopedia

Current revision

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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