1i4e

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==CRYSTAL STRUCTURE OF THE CASPASE-8/P35 COMPLEX==
==CRYSTAL STRUCTURE OF THE CASPASE-8/P35 COMPLEX==
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<StructureSection load='1i4e' size='340' side='right' caption='[[1i4e]], [[Resolution|resolution]] 3.00&Aring;' scene=''>
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<StructureSection load='1i4e' size='340' side='right'caption='[[1i4e]], [[Resolution|resolution]] 3.00&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[1i4e]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Autographa_californica_nucleopolyhedrovirus Autographa californica nucleopolyhedrovirus] and [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1I4E OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1I4E FirstGlance]. <br>
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<table><tr><td colspan='2'>[[1i4e]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Autographa_californica_nucleopolyhedrovirus Autographa californica nucleopolyhedrovirus] and [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1I4E OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1I4E FirstGlance]. <br>
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</td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</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]] 3&#8491;</td></tr>
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<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">P35 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=46015 Autographa californica nucleopolyhedrovirus]), CASP8, MCH5 ([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='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene></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-8 Caspase-8], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.22.61 3.4.22.61] </span></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=1i4e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1i4e OCA], [https://pdbe.org/1i4e PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1i4e RCSB], [https://www.ebi.ac.uk/pdbsum/1i4e PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1i4e ProSAT]</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=1i4e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1i4e OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1i4e RCSB], [http://www.ebi.ac.uk/pdbsum/1i4e PDBsum]</span></td></tr>
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</table>
</table>
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== Disease ==
 
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[[http://www.uniprot.org/uniprot/CASP8_HUMAN CASP8_HUMAN]] Defects in CASP8 are the cause of caspase-8 deficiency (CASP8D) [MIM:[http://omim.org/entry/607271 607271]]. CASP8D is a disorder resembling autoimmune lymphoproliferative syndrome (ALPS). It is characterized by lymphadenopathy, splenomegaly, and defective CD95-induced apoptosis of peripheral blood lymphocytes (PBLs). It leads to defects in activation of T-lymphocytes, B-lymphocytes, and natural killer cells leading to immunodeficiency characterized by recurrent sinopulmonary and herpes simplex virus infections and poor responses to immunization.<ref>PMID:12353035</ref>
 
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== Function ==
 
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[[http://www.uniprot.org/uniprot/VP35_NPVAC VP35_NPVAC]] Blocks the insect or worm host cells apoptotic response initiated by the viral infection. Confers protection from cell death in mammalian cells. Acts by blocking the activity of members of the caspase family of proteases. Required for late and very late gene expression. [[http://www.uniprot.org/uniprot/CASP8_HUMAN CASP8_HUMAN]] Most upstream protease of the activation cascade of caspases responsible for the TNFRSF6/FAS mediated and TNFRSF1A induced cell death. Binding to the adapter molecule FADD recruits it to either receptor. The resulting aggregate called death-inducing signaling complex (DISC) performs CASP8 proteolytic activation. The active dimeric enzyme is then liberated from the DISC and free to activate downstream apoptotic proteases. Proteolytic fragments of the N-terminal propeptide (termed CAP3, CAP5 and CAP6) are likely retained in the DISC. Cleaves and activates CASP3, CASP4, CASP6, CASP7, CASP9 and CASP10. May participate in the GZMB apoptotic pathways. Cleaves ADPRT. Hydrolyzes the small-molecule substrate, Ac-Asp-Glu-Val-Asp-|-AMC. Likely target for the cowpox virus CRMA death inhibitory protein. Isoform 5, isoform 6, isoform 7 and isoform 8 lack the catalytic site and may interfere with the pro-apoptotic activity of the complex.<ref>PMID:12010809</ref> <ref>PMID:9006941</ref>
 
== Evolutionary Conservation ==
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
Check<jmol>
<jmolCheckbox>
<jmolCheckbox>
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<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/i4/1i4e_consurf.spt"</scriptWhenChecked>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/i4/1i4e_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
<text>to colour the structure by Evolutionary Conservation</text>
<text>to colour the structure by Evolutionary Conservation</text>
</jmolCheckbox>
</jmolCheckbox>
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</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/chain_selection.php?pdb_ID=2ata ConSurf].
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</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1i4e ConSurf].
<div style="clear:both"></div>
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
<div style="background-color:#fffaf0;">
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
</div>
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<div class="pdbe-citations 1i4e" style="background-color:#fffaf0;"></div>
==See Also==
==See Also==
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*[[Caspase|Caspase]]
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*[[Caspase 3D structures|Caspase 3D structures]]
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*[[User:Christopher French|User:Christopher French]]
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== References ==
== References ==
<references/>
<references/>
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</StructureSection>
</StructureSection>
[[Category: Autographa californica nucleopolyhedrovirus]]
[[Category: Autographa californica nucleopolyhedrovirus]]
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[[Category: Caspase-8]]
 
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Cirilli, M]]
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[[Category: Large Structures]]
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[[Category: Huang, Y]]
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[[Category: Cirilli M]]
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[[Category: Myszka, D G]]
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[[Category: Huang Y]]
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[[Category: Rich, R L]]
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[[Category: Myszka DG]]
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[[Category: Wu, H]]
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[[Category: Rich RL]]
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[[Category: Xu, G]]
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[[Category: Wu H]]
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[[Category: Apoptosis-hydrolase complex]]
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[[Category: Xu G]]
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[[Category: Covalent complex protease-inhibitor]]
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Current revision

CRYSTAL STRUCTURE OF THE CASPASE-8/P35 COMPLEX

PDB ID 1i4e

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