4yoc

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'''Unreleased structure'''
 
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The entry 4yoc is ON HOLD until Paper Publication
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==Crystal Structure of human DNMT1 and USP7/HAUSP complex==
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<StructureSection load='4yoc' size='340' side='right'caption='[[4yoc]], [[Resolution|resolution]] 2.92&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[4yoc]] 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=4YOC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4YOC 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]] 2.916&#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=ZN:ZINC+ION'>ZN</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=4yoc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4yoc OCA], [https://pdbe.org/4yoc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4yoc RCSB], [https://www.ebi.ac.uk/pdbsum/4yoc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4yoc ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/UBP7_HUMAN UBP7_HUMAN] Hydrolase that deubiquitinates target proteins such as FOXO4, p53/TP53, MDM2, ERCC6, DNMT1, UHRF1, PTEN and DAXX. Together with DAXX, prevents MDM2 self-ubiquitination and enhances the E3 ligase activity of MDM2 towards p53/TP53, thereby promoting p53/TP53 ubiquitination and proteasomal degradation. Deubiquitinates p53/TP53 and MDM2 and strongly stabilizes p53/TP53 even in the presence of excess MDM2, and also induces p53/TP53-dependent cell growth repression and apoptosis. Deubiquitination of FOXO4 in presence of hydrogen peroxide is not dependent on p53/TP53 and inhibits FOXO4-induced transcriptional activity. In association with DAXX, is involved in the deubiquitination and translocation of PTEN from the nucleus to the cytoplasm, both processes that are counteracted by PML. Involved in cell proliferation during early embryonic development. Involved in transcription-coupled nucleotide excision repair (TC-NER) in response to UV damage: recruited to DNA damage sites following interaction with KIAA1530/UVSSA and promotes deubiquitination of ERCC6, preventing UV-induced degradation of ERCC6. Contributes to the overall stabilization and trans-activation capability of the herpesvirus 1 trans-acting transcriptional protein ICP0/VMW110 during HSV-1 infection. Involved in maintenance of DNA methylation via its interaction with UHRF1 and DNMT1: acts by mediating deubiquitination of UHRF1 and DNMT1, preventing their degradation and promoting DNA methylation by DNMT1. Exhibits a preference towards 'Lys-48'-linked Ubiquitin chains.<ref>PMID:11923872</ref> <ref>PMID:14506283</ref> <ref>PMID:15053880</ref> <ref>PMID:16160161</ref> <ref>PMID:16964248</ref> <ref>PMID:18716620</ref> <ref>PMID:18590780</ref> <ref>PMID:20153724</ref> <ref>PMID:21745816</ref> <ref>PMID:22411829</ref> <ref>PMID:22689415</ref> <ref>PMID:22466611</ref> <ref>PMID:22466612</ref>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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DNMT1 is an important epigenetic regulator that plays a key role in the maintenance of DNA methylation. Here we determined the crystal structure of DNMT1 in complex with USP7 at 2.9 A resolution. The interaction between the two proteins is primarily mediated by an acidic pocket in USP7 and Lysine residues within DNMT1's KG linker. This intermolecular interaction is required for USP7-mediated stabilization of DNMT1. Acetylation of the KG linker Lysine residues impair DNMT1-USP7 interaction and promote the degradation of DNMT1. Treatment with HDAC inhibitors results in an increase in acetylated DNMT1 and decreased total DNMT1 protein. This negative correlation is observed in differentiated neuronal cells and pancreatic cancer cells. Our studies reveal that USP7-mediated stabilization of DNMT1 is regulated by acetylation and provide a structural basis for the design of inhibitors, targeting the DNMT1-USP7 interaction surface for therapeutic applications.
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Authors: Cheng, J., Yang, H., Fang, J., Gong, R., Wang, P., Li, Z., Xu, Y.
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Molecular mechanism for USP7-mediated DNMT1 stabilization by acetylation.,Cheng J, Yang H, Fang J, Ma L, Gong R, Wang P, Li Z, Xu Y Nat Commun. 2015 May 11;6:7023. doi: 10.1038/ncomms8023. PMID:25960197<ref>PMID:25960197</ref>
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Description: Crystal Structure of human DNMT1 and USP7/HAUSP complex
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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: Cheng, J]]
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<div class="pdbe-citations 4yoc" style="background-color:#fffaf0;"></div>
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[[Category: Xu, Y]]
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[[Category: Gong, R]]
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==See Also==
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[[Category: Yang, H]]
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*[[DNA methyltransferase 3D structures|DNA methyltransferase 3D structures]]
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[[Category: Wang, P]]
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*[[Thioesterase 3D structures|Thioesterase 3D structures]]
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[[Category: Fang, J]]
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== References ==
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[[Category: Li, Z]]
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<references/>
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__TOC__
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</StructureSection>
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[[Category: Homo sapiens]]
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[[Category: Large Structures]]
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[[Category: Cheng J]]
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[[Category: Fang J]]
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[[Category: Gong R]]
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[[Category: Li Z]]
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[[Category: Wang P]]
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[[Category: Xu Y]]
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[[Category: Yang H]]

Current revision

Crystal Structure of human DNMT1 and USP7/HAUSP complex

PDB ID 4yoc

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