9zu4: Difference between revisions

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'''Unreleased structure'''


The entry 9zu4 is ON HOLD  until Paper Publication
==Crystal structure of BRD9 bromodomain bound to BZ2==
<StructureSection load='9zu4' size='340' side='right'caption='[[9zu4]], [[Resolution|resolution]] 1.05&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[9zu4]] 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=9ZU4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9ZU4 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]] 1.05&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=XHK:6-[[4-(2-azanylethyl)phenyl]amino]-5-chloranyl-3-methyl-pyrimidin-4-one'>XHK</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=9zu4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9zu4 OCA], [https://pdbe.org/9zu4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9zu4 RCSB], [https://www.ebi.ac.uk/pdbsum/9zu4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9zu4 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 ==
Bromodomain PHD finger Transcription Factor (BPTF) is an epigenetic regulator implicated in cancer progression. However, despite its oncogenic significance, highly selective and potent inhibitors of the BPTF bromodomain (BRD) with suitable physicochemical properties are lacking. Previously, we reported BZ1, a submicromolar BPTF inhibitor that has off-target activities. Here, we applied comparative structural biology and molecular modeling to design BZ2, a regioisomer of BZ1 with enhanced selectivity for BPTF over other class I BRDs and class-IV BRDs such as BRD7 and BRD9. Crystal structures and computational analyses reveal that differential engagement of water networks and polar interactions drives this selectivity. Functional studies demonstrate that genetic disruption of the BPTF BRD or treatment with BZ2 suppresses neuroblastoma (NB) cell growth. With high potency and improved physicochemical properties, BZ2 provides a valuable tool for probing the biology of BPTF and represents a promising starting point for advancing BPTF-targeted drug development.


Authors:  
Differential Water Networks Guide Selectivity Optimization of a Cell Active BPTF Inhibitor in Neuroblastoma.,Babu K, Tsou CJ, Das S, Fan L, Pal A, Sneddon M, Stachowski TR, Samanta P, Nithianantham S, Buchholz C, Zhang S, Fu X, Kathayat RS, Lin W, Li Y, Yang L, Chen T, Fischer M, Shelat AA, Pomerantz WCK Angew Chem Int Ed Engl. 2026 Sep 8:e4580510. doi: 10.1002/anie.4580510. PMID:42711825<ref>PMID:42711825</ref>


Description:  
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
[[Category: Unreleased Structures]]
</div>
<div class="pdbe-citations 9zu4" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Babu K]]
[[Category: Fischer M]]
[[Category: Stachowski TR]]
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