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| | ==Caspase-7 in Complex with DARPin D7.18== | | ==Caspase-7 in Complex with DARPin D7.18== |
| - | <StructureSection load='4lsz' size='340' side='right' caption='[[4lsz]], [[Resolution|resolution]] 2.26Å' scene=''> | + | <StructureSection load='4lsz' size='340' side='right'caption='[[4lsz]], [[Resolution|resolution]] 2.26Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4lsz]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human] and [http://en.wikipedia.org/wiki/Synthetic_construct_sequences Synthetic construct sequences]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4LSZ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4LSZ FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4lsz]] 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=4LSZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4LSZ FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3ibc|3ibc]], [[2p2c|2p2c]]</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=4lsz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4lsz OCA], [https://pdbe.org/4lsz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4lsz RCSB], [https://www.ebi.ac.uk/pdbsum/4lsz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4lsz ProSAT]</span></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>
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| - | <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>
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| - | <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=4lsz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4lsz OCA], [http://pdbe.org/4lsz PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4lsz RCSB], [http://www.ebi.ac.uk/pdbsum/4lsz PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4lsz 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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| | </div> | | </div> |
| | <div class="pdbe-citations 4lsz" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 4lsz" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Caspase 3D structures|Caspase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Caspase-7]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Human]] | + | [[Category: Large Structures]] |
| - | [[Category: Synthetic construct sequences]] | + | [[Category: Synthetic construct]] |
| - | [[Category: Fluetsch, A]] | + | [[Category: Fluetsch A]] |
| - | [[Category: Gruetter, M G]] | + | [[Category: Gruetter MG]] |
| - | [[Category: Lukarska, M]] | + | [[Category: Lukarska M]] |
| - | [[Category: Complex structure]]
| + | |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Selected and specific darpin d7 18]]
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| 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 play important roles during apoptosis, inflammation and proliferation. The high homology among family members makes selective targeting of individual caspases difficult, which is necessary to precisely define the role of these enzymes. We have selected caspase-7-specific binders from a library of DARPins (designed ankyrin repeat proteins). The DARPins D7.18 and D7.43 bind specifically to procaspase 7 and active caspase 7, but not to other members of the family. Binding of the DARPins does not affect the active enzyme, but interferes with its activation by other caspases. The crystal structure of the caspase 7-D7.18 complex elucidates the high selectivity and the mode of inhibition. Combining these caspase-7-specific DARPins with the previously reported caspase-3-inhibitory DARPin D3.4S76R reduces the activity of caspase 3 and 7 in double-transfected HeLa cells during apoptosis. In addition, these cells showed less susceptibility to TRAIL (tumour-necrosis-factor-related apoptosis-inducing ligand)-induced apoptosis in living cell experiments. D7.18 and D7.43 are therefore novel tools for in vitro studies on procaspase 7 activation as well as for clarifying the role of its activation in different cellular processes. If applied in combination with D3.4S76R, they represent an excellent instrument to increase our understanding of these enzymes during various cellular processes.
Combined inhibition of caspase 3 and caspase 7 by two highly selective DARPins slows down cellular demise.,Flutsch A, Ackermann R, Schroeder T, Lukarska M, Hausammann GJ, Weinert C, Briand C, Grutter MG Biochem J. 2014 Jul 15;461(2):279-90. doi: 10.1042/BJ20131456. PMID:24779913[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Flutsch A, Ackermann R, Schroeder T, Lukarska M, Hausammann GJ, Weinert C, Briand C, Grutter MG. Combined inhibition of caspase 3 and caspase 7 by two highly selective DARPins slows down cellular demise. Biochem J. 2014 Jul 15;461(2):279-90. doi: 10.1042/BJ20131456. PMID:24779913 doi:http://dx.doi.org/10.1042/BJ20131456
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