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3s8e

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[[Image:3s8e.jpg|left|200px]]
 
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==Phosphorylation regulates assembly of the caspase-6 substrate-binding groove==
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The line below this paragraph, containing "STRUCTURE_3s8e", creates the "Structure Box" on the page.
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<StructureSection load='3s8e' size='340' side='right'caption='[[3s8e]], [[Resolution|resolution]] 2.88&Aring;' scene=''>
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You may change the PDB parameter (which sets the PDB file loaded into the applet)
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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'>[[3s8e]] 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=3S8E OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3S8E 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]] 2.88&#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=3s8e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3s8e OCA], [https://pdbe.org/3s8e PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3s8e RCSB], [https://www.ebi.ac.uk/pdbsum/3s8e PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3s8e ProSAT]</span></td></tr>
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{{STRUCTURE_3s8e| PDB=3s8e | 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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Caspases, a family of apoptotic proteases, are increasingly recognized as being extensively phosphorylated, usually leading to inactivation. To date, no structural mechanism for phosphorylation-based caspase inactivation is available, although this information may be key to achieving caspase-specific inhibition. Caspase-6 has recently been implicated in neurodegenerative conditions including Huntington's and Alzheimer's diseases. A full understanding of caspase-6 regulation is crucial to caspase-6-specific inhibition. Caspase-6 is phosphorylated by ARK5 kinase at serine 257 leading to suppression of cell death via caspase-6 inhibition. Our structure of the fully inactive phosphomimetic S257D reveals that phosphorylation results in a steric clash with P201 in the L2' loop. Removal of the proline side chain alleviates the clash resulting in nearly wild-type activity levels. This phosphomimetic-mediated steric clash causes misalignment of the substrate-binding groove, preventing substrate binding. Substrate-binding loop misalignment appears to be a widely used regulatory strategy among caspases and may present a new paradigm for caspase-specific control.
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===Phosphorylation regulates assembly of the caspase-6 substrate-binding groove===
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Phosphorylation regulates assembly of the caspase-6 substrate-binding groove.,Velazquez-Delgado EM, Hardy JA Structure. 2012 Apr 4;20(4):742-51. Epub 2012 Apr 3. PMID:22483120<ref>PMID:22483120</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 3s8e" style="background-color:#fffaf0;"></div>
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==About this Structure==
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==See Also==
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[[3s8e]] is a 8 chain structure 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=3S8E OCA].
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*[[Caspase 3D structures|Caspase 3D structures]]
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[[Category: Caspase-6]]
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== References ==
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<references/>
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__TOC__
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Hardy, J A.]]
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[[Category: Large Structures]]
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[[Category: Velazquez-Delgado, E M.]]
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[[Category: Hardy JA]]
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[[Category: Alzheimers']]
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[[Category: Velazquez-Delgado EM]]
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[[Category: Apoptosis]]
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[[Category: Cancer]]
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[[Category: Caspase]]
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[[Category: Cytosol]]
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[[Category: Huntingtons']]
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[[Category: Hydrolase]]
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[[Category: Phosphomimetic]]
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[[Category: Protease]]
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[[Category: Zymogen]]
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Current revision

Phosphorylation regulates assembly of the caspase-6 substrate-binding groove

PDB ID 3s8e

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