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==N-TERMINAL BROMODOMAIN OF HUMAN BRD2 WITH N-cyclopentyl-5-(3,5- dimethyl-1,2-oxazol-4-yl)-2-methylbenzene-1-sulfonamide== | ==N-TERMINAL BROMODOMAIN OF HUMAN BRD2 WITH N-cyclopentyl-5-(3,5- dimethyl-1,2-oxazol-4-yl)-2-methylbenzene-1-sulfonamide== | ||
<StructureSection load='4a9m' size='340' side='right' caption='[[4a9m]], [[Resolution|resolution]] 2.06Å' scene=''> | <StructureSection load='4a9m' size='340' side='right' caption='[[4a9m]], [[Resolution|resolution]] 2.06Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4a9m]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/ | <table><tr><td colspan='2'>[[4a9m]] is a 3 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=4A9M OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4A9M FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=P9M:N-CYCLOPENTYL-5-(3,5-DIMETHYLISOXAZOL-4-YL)-2-METHYLBENZENESULFONAMIDE'>P9M</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=P9M:N-CYCLOPENTYL-5-(3,5-DIMETHYLISOXAZOL-4-YL)-2-METHYLBENZENESULFONAMIDE'>P9M</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> | ||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2yek|2yek]], [[4a9e|4a9e]], [[1x0j|1x0j]], [[4a9f|4a9f]], [[2ydw|2ydw]], [[4a9j|4a9j]], [[4a9i|4a9i]]</td></tr> | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2yek|2yek]], [[4a9e|4a9e]], [[1x0j|1x0j]], [[4a9f|4a9f]], [[2ydw|2ydw]], [[4a9j|4a9j]], [[4a9i|4a9i]]</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=4a9m FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4a9m OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4a9m RCSB], [http://www.ebi.ac.uk/pdbsum/4a9m 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=4a9m FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4a9m OCA], [http://pdbe.org/4a9m PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4a9m RCSB], [http://www.ebi.ac.uk/pdbsum/4a9m PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4a9m ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
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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 4a9m" 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: Bamborough, P]] | [[Category: Bamborough, P]] | ||
[[Category: Chung, C]] | [[Category: Chung, C]] | ||
Revision as of 15:05, 4 August 2016
N-TERMINAL BROMODOMAIN OF HUMAN BRD2 WITH N-cyclopentyl-5-(3,5- dimethyl-1,2-oxazol-4-yl)-2-methylbenzene-1-sulfonamideN-TERMINAL BROMODOMAIN OF HUMAN BRD2 WITH N-cyclopentyl-5-(3,5- dimethyl-1,2-oxazol-4-yl)-2-methylbenzene-1-sulfonamide
Structural highlights
Function[BRD2_HUMAN] May play a role in spermatogenesis or folliculogenesis (By similarity). Binds hyperacetylated chromatin and plays a role in the regulation of transcription, probably by chromatin remodeling. Regulates transcription of the CCND1 gene. Plays a role in nucleosome assembly.[1] Publication Abstract from PubMedBromodomains are epigenetic reader modules that regulate gene transcription through their recognition of acetyl-lysine modified histone tails. Inhibitors of this protein-protein interaction have the potential to modulate multiple diseases as demonstrated by the profound anti-inflammatory and antiproliferative effects of a recently disclosed class of BET compounds. While these compounds were discovered using phenotypic assays, here we present a highly efficient alternative approach to find new chemical templates, exploiting the abundant structural knowledge that exists for this target class. A phenyl dimethyl isoxazole chemotype resulting from a focused fragment screen has been rapidly optimized through structure-based design, leading to a sulfonamide series showing anti-inflammatory activity in cellular assays. This proof-of-principle experiment demonstrates the tractability of the BET family and bromodomain target class to fragment-based hit discovery and structure-based lead optimization. Fragment-based discovery of bromodomain inhibitors part 2: optimization of phenylisoxazole sulfonamides.,Bamborough P, Diallo H, Goodacre JD, Gordon L, Lewis A, Seal JT, Wilson DM, Woodrow MD, Chung CW J Med Chem. 2012 Jan 26;55(2):587-96. Epub 2012 Jan 11. PMID:22136469[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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