View source for 6swp


==C-TERMINAL BROMODOMAIN OF HUMAN BRD2 WITH iBET-BD2 (GSK046)==
<StructureSection load='6swp' size='340' side='right'caption='[[6swp]], [[Resolution|resolution]] 1.60&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6swp]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6SWP OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6SWP FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=LW5:4-acetamido-3-fluoranyl-~{N}-(4-oxidanylcyclohexyl)-5-[(1~{S})-1-phenylethoxy]benzamide'>LW5</scene></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=6swp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6swp OCA], [http://pdbe.org/6swp PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6swp RCSB], [http://www.ebi.ac.uk/pdbsum/6swp PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6swp ProSAT]</span></td></tr>
</table>
== 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>  
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The two tandem bromodomains of the BET proteins enable chromatin binding to facilitate transcription. Drugs that inhibit both bromodomains equally have shown efficacy in certain malignant and inflammatory conditions. To explore the individual functional contributions of the first (BD1) and second (BD2) bromodomains in biology and therapy, we developed selective BD1 and BD2 inhibitors. We found that steady-state gene expression primarily requires BD1 whereas the rapid increase of gene expression induced by inflammatory stimuli requires both BD1 and BD2 of all BET proteins. BD1 inhibitors phenocopied the effects of pan-BET inhibitors in cancer models whereas BD2 inhibitors were predominantly effective in models of inflammatory and autoimmune disease. These insights into the differential requirement of BD1 and BD2 for the maintenance and induction of gene expression may guide future BET targeted therapies.

Selective targeting of BD1 and BD2 of the BET proteins in cancer and immuno-inflammation.,Gilan O, Rioja I, Knezevic K, Bell MJ, Yeung MM, Harker NR, Lam EYN, Chung CW, Bamborough P, Petretich M, Urh M, Atkinson SJ, Bassil AK, Roberts EJ, Vassiliadis D, Burr ML, Preston AGS, Wellaway C, Werner T, Gray JR, Michon AM, Gobbetti T, Kumar V, Soden PE, Haynes A, Vappiani J, Tough DF, Taylor S, Dawson SJ, Bantscheff M, Lindon M, Drewes G, Demont EH, Daniels DL, Grandi P, Prinjha RK, Dawson MA Science. 2020 Mar 19. pii: science.aaz8455. doi: 10.1126/science.aaz8455. PMID:32193360<ref>PMID:32193360</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6swp" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Chung, C]]
[[Category: Antagonist]]
[[Category: Brd2]]
[[Category: Bromodomain]]
[[Category: Bromodomain containing protein 2]]
[[Category: Epigenetic reader]]
[[Category: Histone]]
[[Category: Inhibitor]]
[[Category: Transcription]]