View source for 3s8e

==Phosphorylation regulates assembly of the caspase-6 substrate-binding groove==
<StructureSection load='3s8e' size='340' side='right' caption='[[3s8e]], [[Resolution|resolution]] 2.88&Aring;' scene=''>
== Structural highlights ==
<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>
</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>
<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>
<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>
<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>
</table>
== Function ==
[[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. 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
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.

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>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>

==See Also==
*[[Caspase|Caspase]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Caspase-6]]
[[Category: Homo sapiens]]
[[Category: Hardy, J A]]
[[Category: Velazquez-Delgado, E M]]
[[Category: Alzheimers']]
[[Category: Apoptosis]]
[[Category: Cancer]]
[[Category: Caspase]]
[[Category: Cytosol]]
[[Category: Huntingtons']]
[[Category: Hydrolase]]
[[Category: Phosphomimetic]]
[[Category: Protease]]
[[Category: Zymogen]]