6ffe: Difference between revisions
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==Human BRD2 C-terminal bromodomain with 2-((4-acetyl-3-cyclopropyl-3,4-dihydroquinoxalin-1(2H)-yl)methyl)benzoic acid== | ==Human BRD2 C-terminal bromodomain with 2-((4-acetyl-3-cyclopropyl-3,4-dihydroquinoxalin-1(2H)-yl)methyl)benzoic acid== | ||
<StructureSection load='6ffe' size='340' side='right' caption='[[6ffe]], [[Resolution|resolution]] 1.76Å' scene=''> | <StructureSection load='6ffe' size='340' side='right'caption='[[6ffe]], [[Resolution|resolution]] 1.76Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[6ffe]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6FFE OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6FFE FirstGlance]. <br> | <table><tr><td colspan='2'>[[6ffe]] 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=6FFE OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6FFE FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=D7Q:2-((4-acetyl-3-cyclopropyl-3,4-dihydroquinoxalin-1(2H)-yl)methyl)benzoic+acid'>D7Q</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=D7Q:2-((4-acetyl-3-cyclopropyl-3,4-dihydroquinoxalin-1(2H)-yl)methyl)benzoic+acid'>D7Q</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene></td></tr> | ||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[6ffd|6ffd]]</td></tr> | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[6ffd|6ffd]]</td></tr> | ||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">BRD2, KIAA9001, RING3 ([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=6ffe FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ffe OCA], [http://pdbe.org/6ffe PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6ffe RCSB], [http://www.ebi.ac.uk/pdbsum/6ffe PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6ffe ProSAT]</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=6ffe FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ffe OCA], [http://pdbe.org/6ffe PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6ffe RCSB], [http://www.ebi.ac.uk/pdbsum/6ffe PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6ffe ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
[[http://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> | [[http://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 == | |||
The bromodomain and extra-terminal domain (BET) family of proteins bind acetylated lysine residues on histone proteins. The four BET bromodomains-BRD2, BRD3, BRD4, and BRDT-each contain two bromodomain modules. BET bromodomain inhibition is a potential therapy for various cancers and immunoinflammatory diseases, but few reported inhibitors show selectivity within the BET family. Inhibitors with selectivity for the first or second bromodomain are desired to aid investigation of the biological function of these domains. Focused library screening identified a series of tetrahydroquinoxalines with selectivity for the second bromodomains of the BET family (BD2). Structure-guided optimization of the template improved potency, selectivity, and physicochemical properties, culminating in potent BET inhibitors with BD2 selectivity. | |||
Discovery of Tetrahydroquinoxalines as Bromodomain and Extra-Terminal Domain (BET) Inhibitors with Selectivity for the Second Bromodomain.,Law RP, Atkinson SJ, Bamborough P, Chung CW, Demont EH, Gordon LJ, Lindon M, Prinjha RK, Watson AJB, Hirst DJ J Med Chem. 2018 May 24;61(10):4317-4334. doi: 10.1021/acs.jmedchem.7b01666. Epub, 2018 May 3. PMID:29656650<ref>PMID:29656650</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 6ffe" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Bromodomain-containing protein 3D structures|Bromodomain-containing protein 3D structures]] | |||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Human]] | |||
[[Category: Large Structures]] | |||
[[Category: Chung, C]] | [[Category: Chung, C]] | ||
[[Category: Antagonist]] | [[Category: Antagonist]] | ||