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| | <StructureSection load='4iyr' size='340' side='right'caption='[[4iyr]], [[Resolution|resolution]] 2.70Å' scene=''> | | <StructureSection load='4iyr' size='340' side='right'caption='[[4iyr]], [[Resolution|resolution]] 2.70Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4iyr]] 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=4IYR OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4IYR FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4iyr]] 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=4IYR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4IYR FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3nr2|3nr2]], [[3v6l|3v6l]], [[3v6m|3v6m]], [[3od5|3od5]]</td></tr> | + | </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=4iyr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4iyr OCA], [https://pdbe.org/4iyr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4iyr RCSB], [https://www.ebi.ac.uk/pdbsum/4iyr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4iyr ProSAT]</span></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 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='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=4iyr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4iyr OCA], [http://pdbe.org/4iyr PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4iyr RCSB], [http://www.ebi.ac.uk/pdbsum/4iyr PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4iyr ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == 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. | + | [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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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Caspase-6]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Human]]
| + | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Cao, Q]] | + | [[Category: Cao Q]] |
| - | [[Category: Li, L F]] | + | [[Category: Li L-F]] |
| - | [[Category: Su, X D]] | + | [[Category: Su X-D]] |
| - | [[Category: Wang, X J]] | + | [[Category: Wang X-J]] |
| - | [[Category: Caspase fold]]
| + | |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Protease]]
| + | |
| 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 PubMed
Caspase 6 (CASP6) is a neuron degeneration-related protease and is widely considered to be a potential drug-design target against neurodegenerative diseases such as Huntington's disease and Alzheimer's disease. The N-terminal pro-peptide of CASP6, also referred to as the pro-domain, contains 23 residues and its functional role remains elusive. In this study, the crystal structure of a full-length CASP6 zymogen mutant, proCASP6H121A, was solved. Although the pro-domain was flexible in the crystal, without visible electron density, structural analyses combined with biochemical assays revealed that the pro-domain inhibited CASP6 auto-activation by inhibiting intramolecular cleavage at the intersubunit cleavage site TEVD(193) and also by preventing this site from intermolecular cleavage at low protein concentration through a so-called `suicide-protection' mechanism. Further experiments showed that the length of the pro-domain and the side chain of Asn18 played critical roles in suicide protection. These results disclosed a new inhibitory mechanism of CASP6 and shed light on the pathogenesis and therapeutically relevant study of CASP6-related neurodegenerative diseases.
The regulatory mechanism of the caspase 6 pro-domain revealed by crystal structure and biochemical assays.,Cao Q, Wang XJ, Li LF, Su XD Acta Crystallogr D Biol Crystallogr. 2014 Jan;70(Pt 1):58-67. doi:, 10.1107/S1399004713024218. Epub 2013 Dec 24. PMID:24419379[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Cao Q, Wang XJ, Li LF, Su XD. The regulatory mechanism of the caspase 6 pro-domain revealed by crystal structure and biochemical assays. Acta Crystallogr D Biol Crystallogr. 2014 Jan;70(Pt 1):58-67. doi:, 10.1107/S1399004713024218. Epub 2013 Dec 24. PMID:24419379 doi:http://dx.doi.org/10.1107/S1399004713024218
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