7nq8
From Proteopedia
(Difference between revisions)
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==C-TERMINAL BROMODOMAIN OF HUMAN BRD2 WITH N-ethyl-3-(1-methyl-1H-1,2,3-triazol-4-yl)-4-(pyridin-2-ylmethoxy)benzamide== | ==C-TERMINAL BROMODOMAIN OF HUMAN BRD2 WITH N-ethyl-3-(1-methyl-1H-1,2,3-triazol-4-yl)-4-(pyridin-2-ylmethoxy)benzamide== | ||
| - | <StructureSection load='7nq8' size='340' side='right'caption='[[7nq8]]' scene=''> | + | <StructureSection load='7nq8' size='340' side='right'caption='[[7nq8]], [[Resolution|resolution]] 1.60Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7NQ8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7NQ8 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[7nq8]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7NQ8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7NQ8 FirstGlance]. <br> |
| - | </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=7nq8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7nq8 OCA], [https://pdbe.org/7nq8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7nq8 RCSB], [https://www.ebi.ac.uk/pdbsum/7nq8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7nq8 ProSAT]</span></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=UM5:N-ethyl-3-(1-methyl-1H-1,2,3-triazol-4-yl)-4-(pyridin-2-ylmethoxy)benzamide'>UM5</scene></td></tr> |
| + | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[7nq5|7nq5]], [[7nq7|7nq7]]</div></td></tr> | ||
| + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">BRD2, KIAA9001, RING3 ([https://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'>[https://proteopedia.org/fgij/fg.htm?mol=7nq8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7nq8 OCA], [https://pdbe.org/7nq8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7nq8 RCSB], [https://www.ebi.ac.uk/pdbsum/7nq8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7nq8 ProSAT]</span></td></tr> | ||
</table> | </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 == | ||
| + | A number of reports have recently been published describing the discovery and optimization of bromo and extraterminal inhibitors which are selective for the second bromodomain (BD2); these include our own work toward GSK046 (3) and GSK620 (5). This paper describes our approach to mitigating the genotoxicity risk of GSK046 by replacement of the acetamide functionality with a heterocyclic ring. This was followed by a template-hopping and hybridization approach, guided by structure-based drug design, to incorporate learnings from other BD2-selective series, optimize the vector for the amide region, and explore the ZA cleft, leading to the identification of potent, selective, and bioavailable compounds 28 (GSK452), 39 (GSK737), and 36 (GSK217). | ||
| + | |||
| + | Template-Hopping Approach Leads to Potent, Selective, and Highly Soluble Bromo and Extraterminal Domain (BET) Second Bromodomain (BD2) Inhibitors.,Aylott HE, Atkinson SJ, Bamborough P, Bassil A, Chung CW, Gordon L, Grandi P, Gray JRJ, Harrison LA, Hayhow TG, Messenger C, Mitchell D, Phillipou A, Preston A, Prinjha RK, Rianjongdee F, Rioja I, Seal JT, Wall ID, Watson RJ, Woolven JM, Demont EH J Med Chem. 2021 Mar 4. doi: 10.1021/acs.jmedchem.0c02156. PMID:33662213<ref>PMID:33662213</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 7nq8" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| + | [[Category: Human]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
| - | [[Category: Chung | + | [[Category: Chung, C W]] |
| + | [[Category: Antagonist]] | ||
| + | [[Category: Brd2]] | ||
| + | [[Category: Bromodomain]] | ||
| + | [[Category: Bromodomain containing protein 2]] | ||
| + | [[Category: Epigenetic reader]] | ||
| + | [[Category: Histone]] | ||
| + | [[Category: Inhibitor]] | ||
| + | [[Category: Nuclear protein]] | ||
Revision as of 07:16, 7 April 2021
C-TERMINAL BROMODOMAIN OF HUMAN BRD2 WITH N-ethyl-3-(1-methyl-1H-1,2,3-triazol-4-yl)-4-(pyridin-2-ylmethoxy)benzamide
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