1sc3

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[[Image:1sc3.gif|left|200px]]
 
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{{Structure
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==Crystal structure of the human caspase-1 C285A mutant in complex with malonate==
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|PDB= 1sc3 |SIZE=350|CAPTION= <scene name='initialview01'>1sc3</scene>, resolution 1.80&Aring;
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<StructureSection load='1sc3' size='340' side='right'caption='[[1sc3]], [[Resolution|resolution]] 1.80&Aring;' scene=''>
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|SITE=
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== Structural highlights ==
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|LIGAND= <scene name='pdbligand=MLI:MALONATE+ION'>MLI</scene>
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<table><tr><td colspan='2'>[[1sc3]] 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=1SC3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1SC3 FirstGlance]. <br>
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|ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/Caspase-1 Caspase-1], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.22.36 3.4.22.36] </span>
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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]] 1.8&#8491;</td></tr>
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|GENE= CASP1, IL1BC, IL1BCE ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MLI:MALONATE+ION'>MLI</scene></td></tr>
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|DOMAIN=
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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=1sc3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1sc3 OCA], [https://pdbe.org/1sc3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1sc3 RCSB], [https://www.ebi.ac.uk/pdbsum/1sc3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1sc3 ProSAT]</span></td></tr>
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|RELATEDENTRY=[[1sc1|1SC1]], [[1sc4|1SC4]]
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</table>
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|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1sc3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1sc3 OCA], [http://www.ebi.ac.uk/pdbsum/1sc3 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1sc3 RCSB]</span>
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== Function ==
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}}
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[https://www.uniprot.org/uniprot/CASP1_HUMAN CASP1_HUMAN] Thiol protease that cleaves IL-1 beta between an Asp and an Ala, releasing the mature cytokine which is involved in a variety of inflammatory processes. Important for defense against pathogens. Cleaves and activates sterol regulatory element binding proteins (SREBPs). Can also promote apoptosis.<ref>PMID:7876192</ref> <ref>PMID:15498465</ref>
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/sc/1sc3_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</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/main_output.php?pdb_ID=1sc3 ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Caspase-1, a mediator of the posttranslational processing of IL-1beta and IL-18, requires an aspartic acid in the P1 position of its substrates. The mechanisms of caspase-1 activation remain poorly understood despite numerous structures of the enzyme complexed with aspartate-based inhibitors. Here we report a crystal structure of ligand-free caspase-1 that displays dramatic rearrangements of loops defining the active site to generate a closed conformation that is incompatible with substrate binding. A structure of the enzyme complexed with malonate shows the protein in its open (active-site ligand-bound) conformation in which malonate reproduces the hydrogen bonding network observed in structures with covalent inhibitors. These results illustrate the essential function of the obligatory aspartate recognition element that opens the active site of caspase-1 to substrates and may be the determinant responsible for the conformational changes between ligand-free and -bound forms of the enzyme, and suggest a new approach for identifying novel aspartic acid mimetics.
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'''Crystal structure of the human caspase-1 C285A mutant in complex with malonate'''
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Crystal structures of a ligand-free and malonate-bound human caspase-1: implications for the mechanism of substrate binding.,Romanowski MJ, Scheer JM, O'Brien T, McDowell RS Structure. 2004 Aug;12(8):1361-71. PMID:15296730<ref>PMID:15296730</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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<div class="pdbe-citations 1sc3" style="background-color:#fffaf0;"></div>
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==Overview==
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==See Also==
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Caspase-1, a mediator of the posttranslational processing of IL-1beta and IL-18, requires an aspartic acid in the P1 position of its substrates. The mechanisms of caspase-1 activation remain poorly understood despite numerous structures of the enzyme complexed with aspartate-based inhibitors. Here we report a crystal structure of ligand-free caspase-1 that displays dramatic rearrangements of loops defining the active site to generate a closed conformation that is incompatible with substrate binding. A structure of the enzyme complexed with malonate shows the protein in its open (active-site ligand-bound) conformation in which malonate reproduces the hydrogen bonding network observed in structures with covalent inhibitors. These results illustrate the essential function of the obligatory aspartate recognition element that opens the active site of caspase-1 to substrates and may be the determinant responsible for the conformational changes between ligand-free and -bound forms of the enzyme, and suggest a new approach for identifying novel aspartic acid mimetics.
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*[[Caspase 3D structures|Caspase 3D structures]]
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== References ==
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==About this Structure==
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<references/>
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1SC3 is a [[Protein complex]] structure of sequences 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=1SC3 OCA].
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__TOC__
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</StructureSection>
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==Reference==
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Crystal structures of a ligand-free and malonate-bound human caspase-1: implications for the mechanism of substrate binding., Romanowski MJ, Scheer JM, O'Brien T, McDowell RS, Structure. 2004 Aug;12(8):1361-71. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/15296730 15296730]
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[[Category: Caspase-1]]
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[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Protein complex]]
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[[Category: Large Structures]]
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[[Category: Brien, T O.]]
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[[Category: McDowell RS]]
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[[Category: McDowell, R S.]]
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[[Category: O'Brien T]]
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[[Category: Romanowski, M J.]]
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[[Category: Romanowski MJ]]
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[[Category: Scheer, J M.]]
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[[Category: Scheer JM]]
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[[Category: malonate-bound caspase-1]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 23:40:03 2008''
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Current revision

Crystal structure of the human caspase-1 C285A mutant in complex with malonate

PDB ID 1sc3

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