3v6m

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[[Image:3v6m.png|left|200px]]
 
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==Inhibition of caspase-6 activity by single mutation outside the active site==
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The line below this paragraph, containing "STRUCTURE_3v6m", creates the "Structure Box" on the page.
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<StructureSection load='3v6m' size='340' side='right'caption='[[3v6m]], [[Resolution|resolution]] 2.69&Aring;' scene=''>
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== Structural highlights ==
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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<table><tr><td colspan='2'>[[3v6m]] is a 8 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=3V6M OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3V6M 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]] 2.692&#8491;</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=3v6m FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3v6m OCA], [https://pdbe.org/3v6m PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3v6m RCSB], [https://www.ebi.ac.uk/pdbsum/3v6m PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3v6m ProSAT]</span></td></tr>
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{{STRUCTURE_3v6m| PDB=3v6m | SCENE= }}
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/CASP6_HUMAN CASP6_HUMAN] Involved in the activation cascade of caspases responsible for apoptosis execution. Cleaves poly(ADP-ribose) polymerase in vitro, as well as lamins. Overexpression promotes programmed cell death.
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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The apoptotic effector caspase-6 (CASP6) has been clearly identified as a drug target due to its strong association with neurodegeneration and axonal pruning events as well as its crucial roles in Huntington disease and Alzheimer disease. CASP6 activity is suppressed by ARK5-mediated phosphorylation at Ser(257) with an unclear mechanism. In this work, we solved crystal structures of DeltaproCASP6S257E and p20/p10S257E, which mimicked the phosphorylated CASP6 zymogen and activated CASP6, respectively. The structural investigation combined with extensive biochemical assay and molecular dynamics simulation studies revealed that phosphorylation on Ser(257) inhibited self-activation of CASP6 zymogen by "locking" the enzyme in the TEVD(193)-bound "inhibited state." The structural and biochemical results also showed that phosphorylation on Ser(257) inhibited the CASP6 activity by steric hindrance. These results disclosed the inhibition mechanism of CASP6 phosphorylation and laid the foundation for a new strategy of rational CASP6 drug design.
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===Inhibition of caspase-6 activity by single mutation outside the active site===
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Inhibitory mechanism of caspase-6 phosphorylation revealed by crystal structures, molecular dynamics simulations, and biochemical assays.,Cao Q, Wang XJ, Liu CW, Liu DF, Li LF, Gao YQ, Su XD J Biol Chem. 2012 May 4;287(19):15371-9. Epub 2012 Mar 20. PMID:22433863<ref>PMID:22433863</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 class="pdbe-citations 3v6m" style="background-color:#fffaf0;"></div>
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(as it appears on PubMed at http://www.pubmed.gov), where 22433863 is the PubMed ID number.
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{{ABSTRACT_PUBMED_22433863}}
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==About this Structure==
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[[3v6m]] is a 8 chain structure of [[Caspase]] with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3V6M OCA].
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==See Also==
==See Also==
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*[[Caspase|Caspase]]
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*[[Caspase 3D structures|Caspase 3D structures]]
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== References ==
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==Reference==
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<references/>
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<ref group="xtra">PMID:022433863</ref><references group="xtra"/>
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__TOC__
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[[Category: Caspase-6]]
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Cao, Q.]]
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[[Category: Large Structures]]
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[[Category: Li, L F.]]
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[[Category: Cao Q]]
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[[Category: Liu, D F.]]
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[[Category: Li LF]]
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[[Category: Su, X D.]]
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[[Category: Liu DF]]
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[[Category: Wang, X J.]]
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[[Category: Su XD]]
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[[Category: Caspase domain]]
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[[Category: Wang XJ]]
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[[Category: Hydrolase]]
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Current revision

Inhibition of caspase-6 activity by single mutation outside the active site

PDB ID 3v6m

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