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 [http://en.wikipedia.org/wiki/ | <table><tr><td colspan='2'>[[3v6l]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. 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 [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3V6L FirstGlance]. <br> | ||
</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3v6m|3v6m]], [[3nr2|3nr2]], [[3od5|3od5]]</td></tr> | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3v6m|3v6m]], [[3nr2|3nr2]], [[3od5|3od5]]</td></tr> | ||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CASP6 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CASP6 ([http://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'>[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='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=3v6l FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3v6l OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3v6l RCSB], [http://www.ebi.ac.uk/pdbsum/3v6l PDBsum]</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=3v6l FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3v6l OCA], [http://pdbe.org/3v6l PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3v6l RCSB], [http://www.ebi.ac.uk/pdbsum/3v6l PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3v6l ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
</div> | </div> | ||
<div class="pdbe-citations 3v6l" style="background-color:#fffaf0;"></div> | |||
==See Also== | ==See Also== | ||
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</StructureSection> | </StructureSection> | ||
[[Category: Caspase-6]] | [[Category: Caspase-6]] | ||
[[Category: | [[Category: Human]] | ||
[[Category: Cao, Q]] | [[Category: Cao, Q]] | ||
[[Category: Li, L F]] | [[Category: Li, L F]] | ||
Revision as of 01:06, 6 August 2016
Crystal Structure of caspase-6 inactivation mutationCrystal Structure of caspase-6 inactivation mutation
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 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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