7eo5
From Proteopedia
(Difference between revisions)
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==Crystal structure of pyrano 1,3, oxazine derivative in complex with the second bromodomain of BRD2== | ==Crystal structure of pyrano 1,3, oxazine derivative in complex with the second bromodomain of BRD2== | ||
| - | <StructureSection load='7eo5' size='340' side='right'caption='[[7eo5]]' scene=''> | + | <StructureSection load='7eo5' size='340' side='right'caption='[[7eo5]], [[Resolution|resolution]] 2.00Å' 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=7EO5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7EO5 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[7eo5]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7EO5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7EO5 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=7eo5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7eo5 OCA], [https://pdbe.org/7eo5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7eo5 RCSB], [https://www.ebi.ac.uk/pdbsum/7eo5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7eo5 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=BUX:7-chloranyl-2-[(3-chlorophenyl)amino]pyrano[3,4-e][1,3]oxazine-4,5-dione'>BUX</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=7eo5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7eo5 OCA], [https://pdbe.org/7eo5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7eo5 RCSB], [https://www.ebi.ac.uk/pdbsum/7eo5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7eo5 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. | ||
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| + | 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 7eo5" 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: B-mercaptoethanol]] | ||
| + | [[Category: Bet family]] | ||
| + | [[Category: Brd2]] | ||
| + | [[Category: Bromodomain]] | ||
| + | [[Category: Cme]] | ||
| + | [[Category: Transcription]] | ||
Revision as of 07:14, 16 March 2022
Crystal structure of pyrano 1,3, oxazine derivative in complex with the second bromodomain of BRD2
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Categories: Large Structures | Arole, A | Ashok, S | Deshmukh, P | Padmanabhan, B | B-mercaptoethanol | Bet family | Brd2 | Bromodomain | Cme | Transcription
