4qb3

From Proteopedia

(Difference between revisions)

Revision as of 18:38, 1 February 2017

Crystal structure of the first bromodomain of human BRD4 in complex with Olinone

Structural highlights

4qb3 is a 1 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
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

Lysine acetylation regulates gene expression through modulating protein-protein interactions in chromatin. Chemical inhibition of acetyl-lysine binding bromodomains of the major chromatin regulators BET (bromodomain and extraterminal domain) proteins has been shown to effectively block cell proliferation in cancer and inflammation. However, whether selective inhibition of individual BET bromodomains has distinctive functional consequences remains only partially understood. In this study, we show that selective chemical inhibition of the first bromodomain of BET proteins using our small-molecule inhibitor, Olinone, accelerated the progression of mouse primary oligodendrocyte progenitors toward differentiation, whereas inhibition of both bromodomains of BET proteins hindered differentiation. This effect was target specific, as it was not detected in cells treated with inactive analogs and independent of any effect on proliferation. Therefore, selective chemical modulation of individual bromodomains, rather than use of broad-based inhibitors, may enhance regenerative strategies in disorders characterized by myelin loss such as aging and neurodegeneration.

Selective chemical modulation of gene transcription favors oligodendrocyte lineage progression.,Gacias M, Gerona-Navarro G, Plotnikov AN, Zhang G, Zeng L, Kaur J, Moy G, Rusinova E, Rodriguez Y, Matikainen B, Vincek A, Joshua J, Casaccia P, Zhou MM Chem Biol. 2014 Jul 17;21(7):841-54. doi: 10.1016/j.chembiol.2014.05.009. Epub, 2014 Jun 19. PMID:24954007^[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
↑ Gacias M, Gerona-Navarro G, Plotnikov AN, Zhang G, Zeng L, Kaur J, Moy G, Rusinova E, Rodriguez Y, Matikainen B, Vincek A, Joshua J, Casaccia P, Zhou MM. Selective chemical modulation of gene transcription favors oligodendrocyte lineage progression. Chem Biol. 2014 Jul 17;21(7):841-54. doi: 10.1016/j.chembiol.2014.05.009. Epub, 2014 Jun 19. PMID:24954007 doi:http://dx.doi.org/10.1016/j.chembiol.2014.05.009

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4qb3"

@@ Line 1: / Line 1: @@
 ==Crystal structure of the first bromodomain of human BRD4 in complex with Olinone==
 <StructureSection load='4qb3' size='340' side='right' caption='[[4qb3]], [[Resolution|resolution]] 0.94&Aring;' scene=''>
@@ Line 4: / Line 5: @@
 <table><tr><td colspan='2'>[[4qb3]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4QB3 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4QB3 FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=30M:N-[4-(1-OXO-1,2,3,4-TETRAHYDRO-5H-PYRIDO[4,3-B]INDOL-5-YL)BUTYL]ACETAMIDE'>30M</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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4qb3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4qb3 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4qb3 RCSB], [http://www.ebi.ac.uk/pdbsum/4qb3 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=4qb3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4qb3 OCA], [http://pdbe.org/4qb3 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4qb3 RCSB], [http://www.ebi.ac.uk/pdbsum/4qb3 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4qb3 ProSAT]</span></td></tr>
 </table>
 == Disease ==
@@ Line 18: / Line 19: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 4qb3" style="background-color:#fffaf0;"></div>
 == References ==
 <references/>

4qb3

From Proteopedia

Revision as of 18:38, 1 February 2017

Crystal structure of the first bromodomain of human BRD4 in complex with Olinone

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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