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| | ==Crystal structure of CASPASE-7 in Complex with allosteric inhibitor== | | ==Crystal structure of CASPASE-7 in Complex with allosteric inhibitor== |
| - | <StructureSection load='4fea' size='340' side='right' caption='[[4fea]], [[Resolution|resolution]] 3.79Å' scene=''> | + | <StructureSection load='4fea' size='340' side='right'caption='[[4fea]], [[Resolution|resolution]] 3.79Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4fea]] 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=4FEA OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4FEA FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4fea]] 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=4FEA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4FEA FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=0TE:CHLORO{METHYL+HYDROGENATO(3-)-KAPPA~2~N,S+[PYRIDIN-2-YL(PYRIDIN-2(1H)-YLIDENE-KAPPAN)METHYL]CARBONODITHIOHYDRAZONATE}COPPER'>0TE</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0TE:CHLORO{METHYL+HYDROGENATO(3-)-KAPPA~2~N,S+[PYRIDIN-2-YL(PYRIDIN-2(1H)-YLIDENE-KAPPAN)METHYL]CARBONODITHIOHYDRAZONATE}COPPER'>0TE</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4fdl|4fdl]]</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=4fea FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4fea OCA], [https://pdbe.org/4fea PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4fea RCSB], [https://www.ebi.ac.uk/pdbsum/4fea PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4fea 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>
| + | |
| - | <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=4fea FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4fea OCA], [http://pdbe.org/4fea PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4fea RCSB], [http://www.ebi.ac.uk/pdbsum/4fea PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4fea 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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| | ==See Also== | | ==See Also== |
| - | *[[Caspase|Caspase]] | + | *[[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: Kabaleeswaran, V]] | + | [[Category: Kabaleeswaran V]] |
| - | [[Category: Apoptosis]]
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| - | [[Category: Cysteine protease]]
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| - | [[Category: Hydrolase-hydrolase inhibitor complex]]
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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
Caspase inhibition is a promising approach for treating multiple diseases. Using a reconstituted assay and high-throughput screening, we identified a group of nonpeptide caspase inhibitors. These inhibitors share common chemical scaffolds, suggesting the same mechanism of action. They can inhibit apoptosis in various cell types induced by multiple stimuli; they can also inhibit caspase-1-mediated interleukin generation in macrophages, indicating potential anti-inflammatory application. While these compounds inhibit all the tested caspases, kinetic analysis indicates they do not compete for the catalytic sites of the enzymes. The cocrystal structure of one of these compounds with caspase-7 reveals that it binds to the dimerization interface of the caspase, another common structural element shared by all active caspases. Consistently, biochemical analysis demonstrates that the compound abates caspase-8 dimerization. Based on these kinetic, biochemical, and structural analyses, we suggest that these compounds are allosteric caspase inhibitors that function through binding to the dimerization interface of caspases.
A Class of Allosteric Caspase Inhibitors Identified by High-Throughput Screening.,Feldman T, Kabaleeswaran V, Jang SB, Antczak C, Djaballah H, Wu H, Jiang X Mol Cell. 2012 Jul 10. PMID:22795132[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Feldman T, Kabaleeswaran V, Jang SB, Antczak C, Djaballah H, Wu H, Jiang X. A Class of Allosteric Caspase Inhibitors Identified by High-Throughput Screening. Mol Cell. 2012 Jul 10. PMID:22795132 doi:10.1016/j.molcel.2012.06.007
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