7kxt

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(New page: '''Unreleased structure''' The entry 7kxt is ON HOLD Authors: Zhu, L., Dong, A., Du, D., Liu, Y., Luo, C., Arrowsmith, C.H., Edwards, A.M., Min, J., Structural Genomics Consortium (SGC)...)
Current revision (15:33, 18 October 2023) (edit) (undo)
 
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'''Unreleased structure'''
 
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The entry 7kxt is ON HOLD
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==Crystal structure of human EED==
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<StructureSection load='7kxt' size='340' side='right'caption='[[7kxt]], [[Resolution|resolution]] 2.15&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[7kxt]] 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=7KXT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7KXT FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.15&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=UNX:UNKNOWN+ATOM+OR+ION'>UNX</scene>, <scene name='pdbligand=XB7:1-[(4-fluorophenyl)methyl]-N-{1-[2-(4-methoxyphenyl)ethyl]piperidin-4-yl}-1H-benzimidazol-2-amine'>XB7</scene></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=7kxt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7kxt OCA], [https://pdbe.org/7kxt PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7kxt RCSB], [https://www.ebi.ac.uk/pdbsum/7kxt PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7kxt ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/EED_HUMAN EED_HUMAN] Polycomb group (PcG) protein. Component of the PRC2/EED-EZH2 complex, which methylates 'Lys-9' and 'Lys-27' of histone H3, leading to transcriptional repression of the affected target gene. Also recognizes 'Lys-26' trimethylated histone H1 with the effect of inhibiting PRC2 complex methyltransferase activity on nucleosomal histone H3 'Lys-27', whereas H3 'Lys-27' recognition has the opposite effect, enabling the propagation of this repressive mark. The PRC2/EED-EZH2 complex may also serve as a recruiting platform for DNA methyltransferases, thereby linking two epigenetic repression systems. Genes repressed by the PRC2/EED-EZH2 complex include HOXC8, HOXA9, MYT1 and CDKN2A.<ref>PMID:9584199</ref> <ref>PMID:10581039</ref> <ref>PMID:14532106</ref> <ref>PMID:15385962</ref> <ref>PMID:15231737</ref> <ref>PMID:15225548</ref> <ref>PMID:16357870</ref> <ref>PMID:18285464</ref> <ref>PMID:20974918</ref>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Disruption of EZH2-embryonic ectoderm development (EED) protein-protein interaction (PPI) is a new promising cancer therapeutic strategy. We have previously reported the discovery of astemizole, a small-molecule inhibitor targeting the EZH2-EED PPI. Herein, we report the cocrystal structure of EED in complex with astemizole at 2.15 A. The structure elucidates the detailed binding mode of astemizole to EED and provides a structure-guided design for the discovery of a novel EZH2-EED interaction inhibitor, DC-PRC2in-01, with an affinity Kd of 4.56 muM. DC-PRC2in-01 destabilizes the PRC2 complex, thereby leading to the degradation of PRC2 core proteins and the decrease of global H3K27me3 levels in cancer cells. The proliferation of PRC2-driven lymphomas cells is effectively inhibited, and the cell cycle is arrested in the G0/G1 phase. Together, these data demonstrate that DC-PRC2in-01 could be an effective chemical probe for investigating the PRC2-related physiology and pathology and providing a promising chemical scaffold for further development.
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Authors: Zhu, L., Dong, A., Du, D., Liu, Y., Luo, C., Arrowsmith, C.H., Edwards, A.M., Min, J., Structural Genomics Consortium (SGC)
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Structure-Guided Development of Small-Molecule PRC2 Inhibitors Targeting EZH2-EED Interaction.,Du D, Xu D, Zhu L, Stazi G, Zwergel C, Liu Y, Luo Z, Li Y, Zhang Y, Zhu K, Ding Y, Liu J, Fan S, Zhao K, Zhang N, Kong X, Jiang H, Chen K, Zhao K, Valente S, Min J, Duan W, Luo C J Med Chem. 2021 Jun 24;64(12):8194-8207. doi: 10.1021/acs.jmedchem.0c02261. Epub, 2021 Jun 2. PMID:34077206<ref>PMID:34077206</ref>
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Description: Crystal structure of human EED
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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[[Category: Unreleased Structures]]
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</div>
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[[Category: Arrowsmith, C.H]]
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<div class="pdbe-citations 7kxt" style="background-color:#fffaf0;"></div>
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[[Category: Luo, C]]
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[[Category: Dong, A]]
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==See Also==
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[[Category: Du, D]]
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*[[Polycomb complex proteins 3D structures|Polycomb complex proteins 3D structures]]
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[[Category: Min, J]]
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== References ==
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[[Category: Edwards, A.M]]
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<references/>
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[[Category: Structural Genomics Consortium (Sgc)]]
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__TOC__
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[[Category: Liu, Y]]
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</StructureSection>
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[[Category: Zhu, L]]
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[[Category: Homo sapiens]]
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[[Category: Large Structures]]
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[[Category: Arrowsmith CH]]
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[[Category: Dong A]]
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[[Category: Du D]]
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[[Category: Edwards AM]]
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[[Category: Liu Y]]
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[[Category: Luo C]]
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[[Category: Min J]]
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[[Category: Zhu L]]

Current revision

Crystal structure of human EED

PDB ID 7kxt

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