View source for 9zuk


==Crystal structure of BPTF bromodomain bound to BZ1==
<StructureSection load='9zuk' size='340' side='right'caption='[[9zuk]], [[Resolution|resolution]] 1.35&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[9zuk]] is a 2 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=9ZUK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9ZUK 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]] 1.35&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=A1C4C:5-[[4-(2-azanylethyl)phenyl]amino]-4-chloranyl-2-methyl-pyridazin-3-one'>A1C4C</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=9zuk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9zuk OCA], [https://pdbe.org/9zuk PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9zuk RCSB], [https://www.ebi.ac.uk/pdbsum/9zuk PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9zuk ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/BPTF_HUMAN BPTF_HUMAN] Histone-binding component of NURF (nucleosome-remodeling factor), a complex which catalyzes ATP-dependent nucleosome sliding and facilitates transcription of chromatin. Specifically recognizes H3 tails trimethylated on 'Lys-4' (H3K4me3), which mark transcription start sites of virtually all active genes. May also regulate transcription through direct binding to DNA or transcription factors.
<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.

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>

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