8hn9

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'''Unreleased structure'''
 
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The entry 8hn9 is ON HOLD until Paper Publication
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==Human SIRT3 Recognizing CCNE2K348la peptide==
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<StructureSection load='8hn9' size='340' side='right'caption='[[8hn9]], [[Resolution|resolution]] 3.70&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[8hn9]] is a 3 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=8HN9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8HN9 FirstGlance]. <br>
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=D8R:(2~{S})-2-azanyl-6-[[(2~{R})-2-oxidanylpropanoyl]amino]hexanoic+acid'>D8R</scene>, <scene name='pdbligand=IMD:IMIDAZOLE'>IMD</scene>, <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=8hn9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8hn9 OCA], [https://pdbe.org/8hn9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8hn9 RCSB], [https://www.ebi.ac.uk/pdbsum/8hn9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8hn9 ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/SIR3_HUMAN SIR3_HUMAN] NAD-dependent protein deacetylase. Activates mitochondrial target proteins, including ACSS1, IDH2 and GDH by deacetylating key lysine residues. Contributes to the regulation of the cellular energy metabolism. Important for regulating tissue-specific ATP levels.<ref>PMID:16788062</ref> <ref>PMID:18680753</ref> <ref>PMID:18794531</ref> <ref>PMID:19535340</ref>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Lysine lactylation (Kla) is a recently discovered histone mark derived from metabolic lactate. The NAD(+) -dependent deacetylase SIRT3, which can also catalyze removal of the lactyl moiety from lysine, is expressed at low levels in hepatocellular carcinoma (HCC) and has been suggested to be an HCC tumor suppressor. Here we report that SIRT3 can delactylate non-histone proteins and suppress HCC development. Using SILAC-based quantitative proteomics, we identify cyclin E2 (CCNE2) as one of the lactylated substrates of SIRT3 in HCC cells. Furthermore, our crystallographic study elucidates the mechanism of CCNE2 K348la delactylation by SIRT3. Our results further suggest that lactylated CCNE2 promotes HCC cell growth, while SIRT3 activation by Honokiol induces HCC cell apoptosis and prevents HCC outgrowth in vivo by regulating Kla levels of CCNE2. Together, our results establish a physiological function of SIRT3 as a delactylase that is important for suppressing HCC, and our structural data could be useful for the future design of activators.
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Authors:
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SIRT3-dependent delactylation of cyclin E2 prevents hepatocellular carcinoma growth.,Jin J, Bai L, Wang D, Ding W, Cao Z, Yan P, Li Y, Xi L, Wang Y, Zheng X, Wei H, Ding C, Wang Y EMBO Rep. 2023 May 4;24(5):e56052. doi: 10.15252/embr.202256052. Epub 2023 Mar , 10. PMID:36896611<ref>PMID:36896611</ref>
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Description:
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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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<div class="pdbe-citations 8hn9" style="background-color:#fffaf0;"></div>
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== References ==
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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: Ding W]]
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[[Category: Wang Y]]

Revision as of 06:58, 10 May 2023

Human SIRT3 Recognizing CCNE2K348la peptide

PDB ID 8hn9

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