4a9m: Difference between revisions
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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== | |||
<StructureSection load='4a9m' size='340' side='right'caption='[[4a9m]], [[Resolution|resolution]] 2.06Å' scene=''> | |||
== Structural highlights == | |||
or | <table><tr><td colspan='2'>[[4a9m]] is a 3 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=4A9M OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4A9M FirstGlance]. <br> | ||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.06Å</td></tr> | |||
- | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4a9m FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4a9m OCA], [https://pdbe.org/4a9m PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4a9m RCSB], [https://www.ebi.ac.uk/pdbsum/4a9m PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4a9m ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/BRD2_HUMAN 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.<ref>PMID:18406326</ref> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Bromodomains 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<ref>PMID:22136469</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 4a9m" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Bromodomain-containing protein 3D structures|Bromodomain-containing protein 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
== | |||
[[ | |||
== | |||
< | |||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: | [[Category: Bamborough P]] | ||
[[Category: | [[Category: Chung C]] | ||
Latest revision as of 13:48, 9 May 2024
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
FunctionBRD2_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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