5ji8: Difference between revisions
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==Crystal structure of the BRD9 bromodomain and hit 1== | |||
<StructureSection load='5ji8' size='340' side='right'caption='[[5ji8]], [[Resolution|resolution]] 1.42Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[5ji8]] is a 1 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=5JI8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5JI8 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]] 1.42Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=6KT:2-AMINO-1,3-BENZOTHIAZOLE-6-CARBOXAMIDE'>6KT</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=5ji8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ji8 OCA], [https://pdbe.org/5ji8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5ji8 RCSB], [https://www.ebi.ac.uk/pdbsum/5ji8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5ji8 ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/BRD9_HUMAN BRD9_HUMAN] May play a role in chromatin remodeling and regulation of transcription. | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Complex biology associated with the inhibition of bromodomain and extra-terminal domain (BET) family using chemical probes has attracted increasing attention for the need to identify new non-BET bromodomain (BD) inhibitors. Several potent inhibitors of BRD9 BD have very recently been discovered with anti-cancer and anti-inflammation activity. However, its paralog BRD7 BD remains unexploited. Here, we identify new chemotypes targeting BRD7 BD using NMR fragment-based screening. BRD7/9 BDs exhibit similar patterns of chemical shift perturbations upon the titration of hit 1. The crystal structure demonstrates that hit 1 repels the Y222 group of BRD9 BD in a way similar to butyryllysine but not to the acetyllysine and known inhibitors. Hit 1 induces less rearrangement of residue F161 of BRD9 BD than acetyllysine, butyryllysine and crotonyllysine. Our study provides structural insight into the new generation of butyryllysine mimics for probing the function of BRD7/9 BD. | |||
NMR fragment screening hit induces plasticity of BRD7/9 bromodomains.,Wang N, Li F, Bao H, Li J, Wu J, Ruan K Chembiochem. 2016 May 19. doi: 10.1002/cbic.201600184. PMID:27194508<ref>PMID:27194508</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 5ji8" 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: Bao H]] | |||
[[Category: Li F]] | |||
[[Category: Li J]] | |||
[[Category: Ruan K]] | |||
[[Category: Wang N]] | |||
[[Category: Wu J]] | |||
Latest revision as of 21:52, 20 September 2023
Crystal structure of the BRD9 bromodomain and hit 1Crystal structure of the BRD9 bromodomain and hit 1
Structural highlights
FunctionBRD9_HUMAN May play a role in chromatin remodeling and regulation of transcription. Publication Abstract from PubMedComplex biology associated with the inhibition of bromodomain and extra-terminal domain (BET) family using chemical probes has attracted increasing attention for the need to identify new non-BET bromodomain (BD) inhibitors. Several potent inhibitors of BRD9 BD have very recently been discovered with anti-cancer and anti-inflammation activity. However, its paralog BRD7 BD remains unexploited. Here, we identify new chemotypes targeting BRD7 BD using NMR fragment-based screening. BRD7/9 BDs exhibit similar patterns of chemical shift perturbations upon the titration of hit 1. The crystal structure demonstrates that hit 1 repels the Y222 group of BRD9 BD in a way similar to butyryllysine but not to the acetyllysine and known inhibitors. Hit 1 induces less rearrangement of residue F161 of BRD9 BD than acetyllysine, butyryllysine and crotonyllysine. Our study provides structural insight into the new generation of butyryllysine mimics for probing the function of BRD7/9 BD. NMR fragment screening hit induces plasticity of BRD7/9 bromodomains.,Wang N, Li F, Bao H, Li J, Wu J, Ruan K Chembiochem. 2016 May 19. doi: 10.1002/cbic.201600184. PMID:27194508[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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