View source for 6v0q


==Crystal structure of the bromodomain of human BRD7 bound to TG003==
<StructureSection load='6v0q' size='340' side='right'caption='[[6v0q]], [[Resolution|resolution]] 1.69&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6v0q]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6V0Q OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6V0Q FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.69&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EAE:(1~{Z})-1-(3-ethyl-5-methoxy-1,3-benzothiazol-2-ylidene)propan-2-one'>EAE</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</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=6v0q FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6v0q OCA], [https://pdbe.org/6v0q PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6v0q RCSB], [https://www.ebi.ac.uk/pdbsum/6v0q PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6v0q ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/BRD7_HUMAN BRD7_HUMAN] Acts both as coactivator and as corepressor. May play a role in chromatin remodeling. Activator of the Wnt signaling pathway in a DVL1-dependent manner by negatively regulating the GSK3B phosphotransferase activity. Induces dephosphorylation of GSK3B at 'Tyr-216'. Down-regulates TRIM24-mediated activation of transcriptional activation by AR (By similarity). Transcriptional corepressor that down-regulates the expression of target genes. Binds to target promoters, leading to increased histone H3 acetylation at 'Lys-9' (H3K9ac). Binds to the ESR1 promoter. Recruits BRCA1 and POU2F1 to the ESR1 promoter. Coactivator for TP53-mediated activation of transcription of a set of target genes. Required for TP53-mediated cell-cycle arrest in response to oncogene activation. Promotes acetylation of TP53 at 'Lys-382', and thereby promotes efficient recruitment of TP53 to target promoters. Inhibits cell cycle progression from G1 to S phase.<ref>PMID:16265664</ref> <ref>PMID:16475162</ref> <ref>PMID:20215511</ref> <ref>PMID:20228809</ref> <ref>PMID:20660729</ref> 
<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&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6v0q" style="background-color:#fffaf0;"></div>

==See Also==
*[[Bromodomain-containing protein 3D structures|Bromodomain-containing protein 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Chan A]]
[[Category: Karim MR]]
[[Category: Schonbrunn E]]