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3s8e

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{{STRUCTURE_3s8e| PDB=3s8e | SCENE= }}
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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===
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<StructureSection load='3s8e' size='340' side='right' caption='[[3s8e]], [[Resolution|resolution]] 2.88&Aring;' scene=''>
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{{ABSTRACT_PUBMED_22483120}}
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== Structural highlights ==
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<table><tr><td colspan='2'>[[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]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3S8E FirstGlance]. <br>
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</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2wdp|2wdp]], [[3nkf|3nkf]], [[3nr2|3nr2]], [[3od5|3od5]], [[3k7e|3k7e]]</td></tr>
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<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CASP6, MCH2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
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<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Caspase-6 Caspase-6], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.22.59 3.4.22.59] </span></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3s8e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3s8e OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3s8e RCSB], [http://www.ebi.ac.uk/pdbsum/3s8e PDBsum]</span></td></tr>
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</table>
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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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==Function==
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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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[[http://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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==About this Structure==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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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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</div>
==See Also==
==See Also==
*[[Caspase|Caspase]]
*[[Caspase|Caspase]]
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== References ==
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==Reference==
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<references/>
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<ref group="xtra">PMID:022483120</ref><references group="xtra"/><references/>
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__TOC__
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</StructureSection>
[[Category: Caspase-6]]
[[Category: Caspase-6]]
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Hardy, J A.]]
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[[Category: Hardy, J A]]
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[[Category: Velazquez-Delgado, E M.]]
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[[Category: Velazquez-Delgado, E M]]
[[Category: Alzheimers']]
[[Category: Alzheimers']]
[[Category: Apoptosis]]
[[Category: Apoptosis]]

Revision as of 07:30, 21 December 2014

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

3s8e, resolution 2.88Å

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