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3r5k

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==A designed redox-controlled caspase-7==
==A designed redox-controlled caspase-7==
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<StructureSection load='3r5k' size='340' side='right' caption='[[3r5k]], [[Resolution|resolution]] 2.86&Aring;' scene=''>
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<StructureSection load='3r5k' size='340' side='right'caption='[[3r5k]], [[Resolution|resolution]] 2.86&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[3r5k]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3R5K OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3R5K FirstGlance]. <br>
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<table><tr><td colspan='2'>[[3r5k]] 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=3R5K OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3R5K FirstGlance]. <br>
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=FMT:FORMIC+ACID'>FMT</scene></td></tr>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.86&#8491;</td></tr>
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<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1f1j|1f1j]], [[1i4o|1i4o]], [[1k86|1k86]], [[1k88|1k88]], [[1gqf|1gqf]], [[1kmc|1kmc]], [[1i51|1i51]], [[1shj|1shj]], [[1shl|1shl]], [[2ql5|2ql5]], [[2ql7|2ql7]], [[2ql9|2ql9]], [[2qlb|2qlb]], [[2qlf|2qlf]], [[2qlj|2qlj]], [[3edr|3edr]], [[3h1p|3h1p]], [[3ibc|3ibc]], [[3ibf|3ibf]]</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FMT:FORMIC+ACID'>FMT</scene></td></tr>
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<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 Homo sapiens])</td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3r5k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3r5k OCA], [https://pdbe.org/3r5k PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3r5k RCSB], [https://www.ebi.ac.uk/pdbsum/3r5k PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3r5k ProSAT]</span></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=3r5k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3r5k OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3r5k RCSB], [http://www.ebi.ac.uk/pdbsum/3r5k PDBsum]</span></td></tr>
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</table>
</table>
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<div style="background-color:#fffaf0;">
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== Function ==
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== Publication Abstract from PubMed ==
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[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.
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Caspases are a powerful class of cysteine proteases. Introduction of activated caspases in healthy or cancerous cells results in induction of apoptotic cell death. We have designed and characterized a version of caspase-7 that can be inactivated under oxidizing conditions like those found extracellularly, then reactivated under reducing, intracellular conditions. This version of caspase-7 is allosterically inactivated when two of the substrate-binding loops are locked together via an engineered disulfide. When this disulfide is reduced, the protein regains full function. The inactive loop-locked version of caspase-7 can be readily observed by immunoblotting and by mass spectrometry. The reduced and reactivated form of the enzyme observed crystallographically is the first caspase-7 structure in which the substrate-binding groove is properly ordered even in the absence of an active-site ligand. In the reactivated structure, the catalytic dyad cysteine-histidine are positioned 3.5 A apart in an orientation that is capable of supporting catalysis. This redox-controlled version of caspase-7 is particularly well-suited for targeted cell death in concert with redox-triggered delivery vehicles.
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A designed redox-controlled caspase.,Witkowski WA, Hardy JA Protein Sci. 2011 Jun 14. doi: 10.1002/pro.673. PMID:21674661<ref>PMID:21674661</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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==See Also==
==See Also==
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*[[Caspase|Caspase]]
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*[[Caspase 3D structures|Caspase 3D structures]]
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== References ==
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<references/>
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__TOC__
__TOC__
</StructureSection>
</StructureSection>
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[[Category: Caspase-7]]
 
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Hardy, J A]]
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[[Category: Large Structures]]
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[[Category: Witkowski, W A]]
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[[Category: Hardy JA]]
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[[Category: Apoptosis]]
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[[Category: Witkowski WA]]
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[[Category: Caspase]]
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[[Category: Cystine aspartate protease]]
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[[Category: Hydrolase]]
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[[Category: Protease]]
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[[Category: Thiol protease]]
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[[Category: Zymogen]]
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Current revision

A designed redox-controlled caspase-7

PDB ID 3r5k

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