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| | <StructureSection load='5ic6' size='340' side='right'caption='[[5ic6]], [[Resolution|resolution]] 2.70Å' scene=''> | | <StructureSection load='5ic6' size='340' side='right'caption='[[5ic6]], [[Resolution|resolution]] 2.70Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5ic6]] is a 6 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=5IC6 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5IC6 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5ic6]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5IC6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5IC6 FirstGlance]. <br> |
| - | </td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=MKE:(4S)-4-AMINO-5-OXOHEXANOIC+ACID'>MKE</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.7Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5ic4|5ic4]]</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MKE:(4S)-4-AMINO-5-OXOHEXANOIC+ACID'>MKE</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CASP7, MCH3 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=5ic6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ic6 OCA], [https://pdbe.org/5ic6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5ic6 RCSB], [https://www.ebi.ac.uk/pdbsum/5ic6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5ic6 ProSAT]</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-7 Caspase-7], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.22.60 3.4.22.60] </span></td></tr>
| + | |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=5ic6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ic6 OCA], [http://pdbe.org/5ic6 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5ic6 RCSB], [http://www.ebi.ac.uk/pdbsum/5ic6 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5ic6 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/CASP7_HUMAN CASP7_HUMAN]] Involved in the activation cascade of caspases responsible for apoptosis execution. Cleaves and activates sterol regulatory element binding proteins (SREBPs). Proteolytically cleaves poly(ADP-ribose) polymerase (PARP) at a '216-Asp-|-Gly-217' bond. Overexpression promotes programmed cell death. | + | [https://www.uniprot.org/uniprot/CASP7_HUMAN CASP7_HUMAN] Involved in the activation cascade of caspases responsible for apoptosis execution. Cleaves and activates sterol regulatory element binding proteins (SREBPs). Proteolytically cleaves poly(ADP-ribose) polymerase (PARP) at a '216-Asp-|-Gly-217' bond. 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-7]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Human]]
| + | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Julien, O]] | + | [[Category: Synthetic construct]] |
| - | [[Category: Lee, P S]] | + | [[Category: Julien O]] |
| - | [[Category: Rettenmaier, T J]] | + | [[Category: Lee PS]] |
| - | [[Category: Seaman, J E]] | + | [[Category: Rettenmaier TJ]] |
| - | [[Category: Thomsen, N D]] | + | [[Category: Seaman JE]] |
| - | [[Category: Wells, J A]] | + | [[Category: Thomsen ND]] |
| - | [[Category: Apoptosis]]
| + | [[Category: Wells JA]] |
| - | [[Category: Hydrolase-hydrolase inhibitor complex]]
| + | |
| Structural highlights
Function
CASP7_HUMAN Involved in the activation cascade of caspases responsible for apoptosis execution. Cleaves and activates sterol regulatory element binding proteins (SREBPs). Proteolytically cleaves poly(ADP-ribose) polymerase (PARP) at a '216-Asp-|-Gly-217' bond. Overexpression promotes programmed cell death.
Publication Abstract from PubMed
Caspases are a family of proteases found in all metazoans, including a dozen in humans, that drive the terminal stages of apoptosis as well as other cellular remodeling and inflammatory events. Caspases are named because they are cysteine class enzymes shown to cleave after aspartate residues. In the past decade, we and others have developed unbiased proteomic methods that collectively identified ~2000 native proteins cleaved during apoptosis after the signature aspartate residues. Here, we explore non-aspartate cleavage events and identify 100s of substrates cleaved after glutamate in both human and murine apoptotic samples. The extended consensus sequence patterns are virtually identical for the aspartate and glutamate cleavage sites suggesting they are cleaved by the same caspases. Detailed kinetic analyses of the dominant apoptotic executioner caspases-3 and -7 show that synthetic substrates containing DEVD downward arrow are cleaved only twofold faster than DEVE downward arrow, which is well within the 500-fold range of rates that natural proteins are cut. X-ray crystallography studies confirm that the two acidic substrates bind in virtually the same way to either caspases-3 or -7 with minimal adjustments to accommodate the larger glutamate. Lastly, during apoptosis we found 121 proteins cleaved after serine residues that have been previously annotated to be phosphorylation sites. We found that caspase-3, but not caspase-7, can cleave peptides containing DEVpS downward arrow at only threefold slower rate than DEVD downward arrow, but does not cleave the unphosphorylated serine peptide. There are only a handful of previously reported examples of proteins cleaved after glutamate and none after phosphorserine. Our studies reveal a much greater promiscuity for cleaving after acidic residues and the name 'cacidase' could aptly reflect this broader specificity.Cell Death and Differentiation advance online publication, 1 July 2016; doi:10.1038/cdd.2016.62.
Cacidases: caspases can cleave after aspartate, glutamate and phosphoserine residues.,Seaman JE, Julien O, Lee PS, Rettenmaier TJ, Thomsen ND, Wells JA Cell Death Differ. 2016 Jul 1. doi: 10.1038/cdd.2016.62. PMID:27367566[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Seaman JE, Julien O, Lee PS, Rettenmaier TJ, Thomsen ND, Wells JA. Cacidases: caspases can cleave after aspartate, glutamate and phosphoserine residues. Cell Death Differ. 2016 Jul 1. doi: 10.1038/cdd.2016.62. PMID:27367566 doi:http://dx.doi.org/10.1038/cdd.2016.62
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