7enz: Difference between revisions
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==Crystal structure of Phenanthredinone moiety in complex with the second bromodomain of BRD2 (BRD2-BD2).== | ==Crystal structure of Phenanthredinone moiety in complex with the second bromodomain of BRD2 (BRD2-BD2).== | ||
<StructureSection load='7enz' size='340' side='right'caption='[[7enz]]' scene=''> | <StructureSection load='7enz' size='340' side='right'caption='[[7enz]], [[Resolution|resolution]] 1.70Å' 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=7ENZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7ENZ FirstGlance]. <br> | <table><tr><td colspan='2'>[[7enz]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7ENZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7ENZ 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=7enz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7enz OCA], [https://pdbe.org/7enz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7enz RCSB], [https://www.ebi.ac.uk/pdbsum/7enz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7enz 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=LDR:PHENANTHRIDIN-6(5H)-ONE'>LDR</scene>, <scene name='pdbligand=PGE:TRIETHYLENE+GLYCOL'>PGE</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=7enz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7enz OCA], [https://pdbe.org/7enz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7enz RCSB], [https://www.ebi.ac.uk/pdbsum/7enz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7enz 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 == | |||
The BET (bromodomain and extra-terminal) family of proteins recognize the acetylated histone code on chromatin and play important roles in transcriptional co-regulation. BRD2 and BRD4, which belong to the BET family, are promising drug targets for the management of chronic diseases. The discovery of new scaffold molecules, a pyrano-1,3-oxazine derivative (NSC 328111; NS5) and phenanthridinone-based derivatives (L10 and its core moiety L10a), as inhibitors of BRD2 bromodomains BD1 and BD2, respectively, has recently been reported. The compound NS5 has a significant inhibitory effect on BRD2 in glioblastoma. Here, the crystal structure of BRD2 BD2 in complex with NS5, refined to 2.0 A resolution, is reported. Moreover, as the previously reported crystal structures of the BD1-NS5 complex and the BD2-L10a complex possess moderate electron density corresponding to the respective ligands, the crystal structures of these complexes were re-evaluated using new X-ray data. Together with biochemical studies using wild-type BRD2 BD1 and BD2 and various mutants, it is confirmed that the pyrano-1,3-oxazine and phenanthridinone derivatives are indeed potent inhibitors of BRD2 bromodomains. | |||
Structural investigation of a pyrano-1,3-oxazine derivative and the phenanthridinone core moiety against BRD2 bromodomains.,Arole AH, Deshmukh P, Sridhar A, Padmanabhan B Acta Crystallogr F Struct Biol Commun. 2022 Mar 1;78(Pt 3):119-127. doi:, 10.1107/S2053230X22001066. Epub 2022 Feb 23. PMID:35234137<ref>PMID:35234137</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 7enz" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Arole A]] | [[Category: Arole, A]] | ||
[[Category: Ashok S]] | [[Category: Ashok, S]] | ||
[[Category: Deshmukh P]] | [[Category: Deshmukh, P]] | ||
[[Category: Padmanabhan B]] | [[Category: Padmanabhan, B]] | ||
[[Category: Bet family]] | |||
[[Category: Bet inhibitor]] | |||
[[Category: Brd2-bd1 inhibitor]] | |||
[[Category: Bromodomain inhibitor]] | |||
[[Category: Transcription]] | |||