6v1l: Difference between revisions
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==Crystal structure of the first bromodomain (BD1) of human BRD4 bound to BI9564== | |||
<StructureSection load='6v1l' size='340' side='right'caption='[[6v1l]], [[Resolution|resolution]] 2.10Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[6v1l]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6V1L OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6V1L FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=5U6:4-[4-[(DIMETHYLAMINO)METHYL]-2,5-DIMETHOXY-PHENYL]-2-METHYL-2,7-NAPHTHYRIDIN-1-ONE'>5U6</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=6v1l FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6v1l OCA], [http://pdbe.org/6v1l PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6v1l RCSB], [http://www.ebi.ac.uk/pdbsum/6v1l PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6v1l ProSAT]</span></td></tr> | |||
</table> | |||
== Disease == | |||
[[http://www.uniprot.org/uniprot/BRD4_HUMAN BRD4_HUMAN]] Note=A chromosomal aberration involving BRD4 is found in a rare, aggressive, and lethal carcinoma arising in midline organs of young people. Translocation t(15;19)(q14;p13) with NUT which produces a BRD4-NUT fusion protein.<ref>PMID:12543779</ref> <ref>PMID:11733348</ref> | |||
== Function == | |||
[[http://www.uniprot.org/uniprot/BRD4_HUMAN BRD4_HUMAN]] Plays a role in a process governing chromosomal dynamics during mitosis (By similarity). | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Inhibition of the bromodomain containing protein 9 (BRD9) by small molecules is an attractive strategy to target mutated SWI/SNF chromatin-remodeling complexes in cancer. However, reported BRD9 inhibitors also inhibit the closely related bromodomain-containing protein 7 (BRD7), which has different biological functions. The structural basis for differential potency and selectivity of BRD9 inhibitors is largely unknown because of the lack of structural information on BRD7. Here, we biochemically and structurally characterized diverse inhibitors with varying degrees of potency and selectivity for BRD9 over BRD7. Novel cocrystal structures of BRD7 liganded with new and previously reported inhibitors of five different chemical scaffolds were determined alongside BRD9 and BRD4. We also report the discovery of first-in-class dual bromodomain-kinase inhibitors outside the bromodomain and extraterminal family targeting BRD7 and BRD9. Combined, the data provide a new framework for the development of BRD7/9 inhibitors with improved selectivity or additional polypharmacologic properties. | |||
Structural Basis of Inhibitor Selectivity in the BRD7/9 Subfamily of Bromodomains.,Karim RM, Chan A, Zhu JY, Schonbrunn E J Med Chem. 2020 Mar 6. doi: 10.1021/acs.jmedchem.9b01980. PMID:32091206<ref>PMID:32091206</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 6v1l" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Chan, A]] | |||
[[Category: Karim, M R]] | |||
[[Category: Schonbrunn, E]] | [[Category: Schonbrunn, E]] | ||
[[Category: | [[Category: Bet]] | ||
[[Category: | [[Category: Brd]] | ||
[[Category: Brd4]] | |||
[[Category: Bromosporine]] | |||
[[Category: Gene regulation]] | |||
[[Category: Hunk1]] | |||