3s8e: Difference between revisions
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==Phosphorylation regulates assembly of the caspase-6 substrate-binding groove== | ==Phosphorylation regulates assembly of the caspase-6 substrate-binding groove== | ||
<StructureSection load='3s8e' size='340' side='right' caption='[[3s8e]], [[Resolution|resolution]] 2.88Å' scene=''> | <StructureSection load='3s8e' size='340' side='right'caption='[[3s8e]], [[Resolution|resolution]] 2.88Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[3s8e]] is a 8 chain structure with sequence from [ | <table><tr><td colspan='2'>[[3s8e]] is a 8 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=3S8E OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/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> | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2wdp|2wdp]], [[3nkf|3nkf]], [[3nr2|3nr2]], [[3od5|3od5]], [[3k7e|3k7e]]</div></td></tr> | ||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CASP6, MCH2 ([ | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CASP6, MCH2 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | ||
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[ | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Caspase-6 Caspase-6], with EC number [https://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'>[ | <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> | ||
</table> | </table> | ||
== Function == | == Function == | ||
[[ | [[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. | ||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
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==See Also== | ==See Also== | ||
*[[Caspase|Caspase]] | *[[Caspase 3D structures|Caspase 3D structures]] | ||
== References == | == References == | ||
<references/> | <references/> | ||
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[[Category: Caspase-6]] | [[Category: Caspase-6]] | ||
[[Category: Human]] | [[Category: Human]] | ||
[[Category: Large Structures]] | |||
[[Category: Hardy, J A]] | [[Category: Hardy, J A]] | ||
[[Category: Velazquez-Delgado, E M]] | [[Category: Velazquez-Delgado, E M]] | ||
[[Category: | [[Category: Alzheimerss']] | ||
[[Category: Apoptosis]] | [[Category: Apoptosis]] | ||
[[Category: Cancer]] | [[Category: Cancer]] | ||
[[Category: Caspase]] | [[Category: Caspase]] | ||
[[Category: Cytosol]] | [[Category: Cytosol]] | ||
[[Category: | [[Category: Huntingtonss']] | ||
[[Category: Hydrolase]] | [[Category: Hydrolase]] | ||
[[Category: Phosphomimetic]] | [[Category: Phosphomimetic]] | ||
[[Category: Protease]] | [[Category: Protease]] | ||
[[Category: Zymogen]] | [[Category: Zymogen]] | ||
Revision as of 13:42, 22 June 2022
Phosphorylation regulates assembly of the caspase-6 substrate-binding groovePhosphorylation regulates assembly of the caspase-6 substrate-binding groove
Structural highlights
Function[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. Publication Abstract from PubMedCaspases, 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[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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