3p5o: Difference between revisions
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==Crystal Structure of the First Bromodomain of Human Brd4 in complex with IBET inhibitor== | ==Crystal Structure of the First Bromodomain of Human Brd4 in complex with IBET inhibitor== | ||
<StructureSection load='3p5o' size='340' side='right' caption='[[3p5o]], [[Resolution|resolution]] 1.60Å' scene=''> | <StructureSection load='3p5o' size='340' side='right' caption='[[3p5o]], [[Resolution|resolution]] 1.60Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[3p5o]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/ | <table><tr><td colspan='2'>[[3p5o]] 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=3P5O OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3P5O FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EAM:2-[(4S)-6-(4-CHLOROPHENYL)-8-METHOXY-1-METHYL-4H-[1,2,4]TRIAZOLO[4,3-A][1,4]BENZODIAZEPIN-4-YL]-N-ETHYLACETAMIDE'>EAM</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EAM:2-[(4S)-6-(4-CHLOROPHENYL)-8-METHOXY-1-METHYL-4H-[1,2,4]TRIAZOLO[4,3-A][1,4]BENZODIAZEPIN-4-YL]-N-ETHYLACETAMIDE'>EAM</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</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 | <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=3p5o FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3p5o OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3p5o RCSB], [http://www.ebi.ac.uk/pdbsum/3p5o 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=3p5o FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3p5o OCA], [http://pdbe.org/3p5o PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3p5o RCSB], [http://www.ebi.ac.uk/pdbsum/3p5o PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3p5o ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Disease == | == Disease == | ||
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
</div> | </div> | ||
<div class="pdbe-citations 3p5o" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Bromodomain-containing protein|Bromodomain-containing protein]] | |||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Human]] | ||
[[Category: Chung, C]] | [[Category: Chung, C]] | ||
[[Category: Antagonist]] | [[Category: Antagonist]] | ||
Revision as of 01:14, 5 August 2016
Crystal Structure of the First Bromodomain of Human Brd4 in complex with IBET inhibitorCrystal Structure of the First Bromodomain of Human Brd4 in complex with IBET inhibitor
Structural highlights
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 PubMedInteraction of pathogens with cells of the immune system results in activation of inflammatory gene expression. This response, although vital for immune defence, is frequently deleterious to the host due to the exaggerated production of inflammatory proteins. The scope of inflammatory responses reflects the activation state of signalling proteins upstream of inflammatory genes as well as signal-induced assembly of nuclear chromatin complexes that support mRNA expression. Recognition of post-translationally modified histones by nuclear proteins that initiate mRNA transcription and support mRNA elongation is a critical step in the regulation of gene expression. Here we present a novel pharmacological approach that targets inflammatory gene expression by interfering with the recognition of acetylated histones by the bromodomain and extra terminal domain (BET) family of proteins. We describe a synthetic compound (I-BET) that by 'mimicking' acetylated histones disrupts chromatin complexes responsible for the expression of key inflammatory genes in activated macrophages, and confers protection against lipopolysaccharide-induced endotoxic shock and bacteria-induced sepsis. Our findings suggest that synthetic compounds specifically targeting proteins that recognize post-translationally modified histones can serve as a new generation of immunomodulatory drugs. Suppression of inflammation by a synthetic histone mimic.,Nicodeme E, Jeffrey KL, Schaefer U, Beinke S, Dewell S, Chung CW, Chandwani R, Marazzi I, Wilson P, Coste H, White J, Kirilovsky J, Rice CM, Lora JM, Prinjha RK, Lee K, Tarakhovsky A Nature. 2010 Dec 23;468(7327):1119-23. Epub 2010 Nov 10. PMID:21068722[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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