3v6l: Difference between revisions
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==Crystal Structure of caspase-6 inactivation mutation== | ==Crystal Structure of caspase-6 inactivation mutation== | ||
<StructureSection load='3v6l' size='340' side='right' caption='[[3v6l]], [[Resolution|resolution]] 2.20Å' scene=''> | <StructureSection load='3v6l' size='340' side='right'caption='[[3v6l]], [[Resolution|resolution]] 2.20Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[3v6l]] is a 2 chain structure with sequence from [ | <table><tr><td colspan='2'>[[3v6l]] is a 2 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=3V6L OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3V6L FirstGlance]. <br> | ||
</td></tr><tr id=' | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.2Å</td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3v6l FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3v6l OCA], [https://pdbe.org/3v6l PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3v6l RCSB], [https://www.ebi.ac.uk/pdbsum/3v6l PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3v6l ProSAT]</span></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | |||
</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 == | ||
| Line 22: | Line 20: | ||
==See Also== | ==See Also== | ||
*[[Caspase|Caspase]] | *[[Caspase 3D structures|Caspase 3D structures]] | ||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Homo sapiens]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: Cao | [[Category: Cao Q]] | ||
[[Category: Li | [[Category: Li LF]] | ||
[[Category: Liu | [[Category: Liu DF]] | ||
[[Category: Su | [[Category: Su XD]] | ||
[[Category: Wang | [[Category: Wang XJ]] | ||
Latest revision as of 15:16, 8 November 2023
Crystal Structure of caspase-6 inactivation mutationCrystal Structure of caspase-6 inactivation mutation
Structural highlights
FunctionCASP6_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 PubMedThe 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. 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[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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