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4j3i

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Revision as of 04:40, 5 August 2016

X-ray crystal structure of bromodomain complex to 1.24 A resolution

Structural highlights

4j3i 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:	, ,
Gene:	BRD4, HUNK1 (HUMAN)
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

Increased synthesis of Apolipoprotein A-I (ApoA-I) and HDL is believed to provide a new approach to treating atherosclerosis through the stimulation of reverse cholesterol transport. RVX-208 increases the production of ApoA-I in hepatocytes in vitro, and in vivo in monkeys and humans, which results in increased HDL-C, but the molecular target was not previously reported. Using binding assays and X-ray crystallography, we now show that RVX-208 selectively binds to bromodomains of the BET (Bromodomain and Extra Terminal) family, competing for a site bound by the endogenous ligand, acetylated lysine, and that this accounts for its pharmacological activity. siRNA experiments further suggest that induction of ApoA-I mRNA is mediated by BET family member BRD4. These data indicate that RVX-208 increases ApoA-I production through an epigenetic mechanism and suggests that BET inhibition may be a promising new approach to the treatment of atherosclerosis.

RVX-208, an Inducer of ApoA-I in Humans, Is a BET Bromodomain Antagonist.,McLure KG, Gesner EM, Tsujikawa L, Kharenko OA, Attwell S, Campeau E, Wasiak S, Stein A, White A, Fontano E, Suto RK, Wong NC, Wagner GS, Hansen HC, Young PR PLoS One. 2013 Dec 31;8(12):e83190. doi: 10.1371/journal.pone.0083190. PMID:24391744^[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
↑ McLure KG, Gesner EM, Tsujikawa L, Kharenko OA, Attwell S, Campeau E, Wasiak S, Stein A, White A, Fontano E, Suto RK, Wong NC, Wagner GS, Hansen HC, Young PR. RVX-208, an Inducer of ApoA-I in Humans, Is a BET Bromodomain Antagonist. PLoS One. 2013 Dec 31;8(12):e83190. doi: 10.1371/journal.pone.0083190. PMID:24391744 doi:http://dx.doi.org/10.1371/journal.pone.0083190

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/4j3i"

@@ Line 1: / Line 1: @@
 ==X-ray crystal structure of bromodomain complex to 1.24 A resolution==
 <StructureSection load='4j3i' size='340' side='right' caption='[[4j3i]], [[Resolution|resolution]] 1.24&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=1K0:2-[4-(2-HYDROXYETHOXY)-3,5-DIMETHYLPHENYL]-5,7-DIMETHOXYQUINAZOLIN-4(3H)-ONE'>1K0</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene></td></tr>
 <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">BRD4, HUNK1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=4j3i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4j3i OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4j3i RCSB], [http://www.ebi.ac.uk/pdbsum/4j3i 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=4j3i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4j3i OCA], [http://pdbe.org/4j3i PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4j3i RCSB], [http://www.ebi.ac.uk/pdbsum/4j3i PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4j3i 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 4j3i" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Bromodomain-containing protein|Bromodomain-containing protein]]
 == References ==
 <references/>

4j3i

From Proteopedia

Revision as of 04:40, 5 August 2016

X-ray crystal structure of bromodomain complex to 1.24 A resolution

Structural highlights

Disease

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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