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7lre

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Current revision (15:00, 6 March 2024) (edit) (undo)
 
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<StructureSection load='7lre' size='340' side='right'caption='[[7lre]], [[Resolution|resolution]] 2.76&Aring;' scene=''>
<StructureSection load='7lre' size='340' side='right'caption='[[7lre]], [[Resolution|resolution]] 2.76&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[7lre]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7LRE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7LRE FirstGlance]. <br>
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<table><tr><td colspan='2'>[[7lre]] 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=7LRE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7LRE 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=ZN:ZINC+ION'>ZN</scene></td></tr>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 2.76&#8491;</td></tr>
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<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[7lrc|7lrc]], [[7lrd|7lrd]]</div></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='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">SLFN12 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=7lre FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7lre OCA], [https://pdbe.org/7lre PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7lre RCSB], [https://www.ebi.ac.uk/pdbsum/7lre PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7lre ProSAT]</span></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=7lre FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7lre OCA], [https://pdbe.org/7lre PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7lre RCSB], [https://www.ebi.ac.uk/pdbsum/7lre PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7lre ProSAT]</span></td></tr>
</table>
</table>
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<div style="background-color:#fffaf0;">
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== Function ==
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== Publication Abstract from PubMed ==
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[https://www.uniprot.org/uniprot/SLN12_HUMAN SLN12_HUMAN]
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DNMDP and related compounds, or velcrins, induce complex formation between the phosphodiesterase PDE3A and the SLFN12 protein, leading to a cytotoxic response in cancer cells that express elevated levels of both proteins. The mechanisms by which velcrins induce complex formation, and how the PDE3A-SLFN12 complex causes cancer cell death, are not fully understood. Here, we show that PDE3A and SLFN12 form a heterotetramer stabilized by binding of DNMDP. Interactions between the C-terminal alpha helix of SLFN12 and residues near the active site of PDE3A are required for complex formation, and are further stabilized by interactions between SLFN12 and DNMDP. Moreover, we demonstrate that SLFN12 is an RNase, that PDE3A binding increases SLFN12 RNase activity, and that SLFN12 RNase activity is required for DNMDP response. This new mechanistic understanding will facilitate development of velcrin compounds into new cancer therapies.
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Structure of PDE3A-SLFN12 complex reveals requirements for activation of SLFN12 RNase.,Garvie CW, Wu X, Papanastasiou M, Lee S, Fuller J, Schnitzler GR, Horner SW, Baker A, Zhang T, Mullahoo JP, Westlake L, Hoyt SH, Toetzl M, Ranaghan MJ, de Waal L, McGaunn J, Kaplan B, Piccioni F, Yang X, Lange M, Tersteegen A, Raymond D, Lewis TA, Carr SA, Cherniack AD, Lemke CT, Meyerson M, Greulich H Nat Commun. 2021 Jul 16;12(1):4375. doi: 10.1038/s41467-021-24495-w. PMID:34272366<ref>PMID:34272366</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 7lre" style="background-color:#fffaf0;"></div>
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== References ==
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<references/>
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__TOC__
__TOC__
</StructureSection>
</StructureSection>
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[[Category: Human]]
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[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Large Structures]]
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[[Category: Fuller, J R]]
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[[Category: Fuller JR]]
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[[Category: Garvie, C W]]
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[[Category: Garvie CW]]
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[[Category: Lemke, C T]]
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[[Category: Lemke CT]]
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[[Category: Complex]]
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[[Category: Dnmdp]]
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[[Category: Molecular glue]]
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[[Category: Rna binding protein]]
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[[Category: Velcrin]]
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Current revision

Cryo-EM of the SLFN12-PDE3A complex: SLFN12 body refinement

PDB ID 7lre

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