4up5: Difference between revisions
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==Crystal structure of the Pygo2 PHD finger in complex with the B9L HD1 domain and a chemical fragment== | |||
<StructureSection load='4up5' size='340' side='right'caption='[[4up5]], [[Resolution|resolution]] 1.65Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[4up5]] 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=4UP5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4UP5 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]] 1.65Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=94W:6-METHOXY-1,3-BENZOTHIAZOL-2-AMINE'>94W</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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=4up5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4up5 OCA], [https://pdbe.org/4up5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4up5 RCSB], [https://www.ebi.ac.uk/pdbsum/4up5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4up5 ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/PYGO2_HUMAN PYGO2_HUMAN] Involved in signal transduction through the Wnt pathway.[https://www.uniprot.org/uniprot/BCL9L_HUMAN BCL9L_HUMAN] Transcriptional regulator that acts as an activator. Promotes beta-catenin transcriptional activity. Plays a role in tumorigenesis. Enhances the neoplastic transforming activity of CTNNB1 (By similarity). | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The Pygo-BCL9 complex is a chromatin reader, facilitating beta-catenin-mediated oncogenesis, and is thus emerging as a potential therapeutic target for cancer. Its function relies on two ligand-binding surfaces of Pygo's PHD finger that anchor the histone H3 tail methylated at lysine 4 (H3K4me) with assistance from the BCL9 HD1 domain. Here, we report the first use of fragment-based screening by NMR to identify small molecules that block protein-protein interactions by a PHD finger. This led to the discovery of a set of benzothiazoles that bind to a cleft emanating from the PHD-HD1 interface, as defined by X-ray crystallography. Furthermore, we discovered a benzimidazole that docks into the H3K4me specificity pocket and displaces the native H3K4me peptide from the PHD finger. Our study demonstrates the ligandability of the Pygo-BCL9 complex and uncovers a privileged scaffold as a template for future development of lead inhibitors of oncogenesis. | |||
Competitive Binding of a Benzimidazole to the Histone-Binding Pocket of the Pygo PHD Finger.,Miller TC, Rutherford TJ, Birchall K, Chugh J, Fiedler M, Bienz M ACS Chem Biol. 2014 Oct 24. PMID:25323450<ref>PMID:25323450</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 4up5" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Bienz M]] | |||
[[Category: Birchall K]] | |||
[[Category: Chugh J]] | |||
[[Category: Fiedler M]] | |||
[[Category: Miller TCR]] | |||
[[Category: Rutherford TJ]] | |||
