1sc1

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[[Image:1sc1.png|left|200px]]
 
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==Crystal structure of an active-site ligand-free form of the human caspase-1 C285A mutant==
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The line below this paragraph, containing "STRUCTURE_1sc1", creates the "Structure Box" on the page.
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<StructureSection load='1sc1' size='340' side='right'caption='[[1sc1]], [[Resolution|resolution]] 2.60&Aring;' scene=''>
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You may change the PDB parameter (which sets the PDB file loaded into the applet)
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== Structural highlights ==
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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<table><tr><td colspan='2'>[[1sc1]] 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=1SC1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1SC1 FirstGlance]. <br>
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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]] 2.6&#8491;</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=CL:CHLORIDE+ION'>CL</scene></td></tr>
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{{STRUCTURE_1sc1| PDB=1sc1 | SCENE= }}
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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=1sc1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1sc1 OCA], [https://pdbe.org/1sc1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1sc1 RCSB], [https://www.ebi.ac.uk/pdbsum/1sc1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1sc1 ProSAT]</span></td></tr>
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</table>
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== Function ==
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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/1sc1_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=1sc1 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 an active-site ligand-free form of the human caspase-1 C285A mutant===
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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 1sc1" style="background-color:#fffaf0;"></div>
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==See Also==
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The line below this paragraph, {{ABSTRACT_PUBMED_15296730}}, adds the Publication Abstract to the page
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*[[Caspase 3D structures|Caspase 3D structures]]
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(as it appears on PubMed at http://www.pubmed.gov), where 15296730 is the PubMed ID number.
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== References ==
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<references/>
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{{ABSTRACT_PUBMED_15296730}}
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__TOC__
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</StructureSection>
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==About this Structure==
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1SC1 is a 2 chains 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=1SC1 OCA].
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==Reference==
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<ref group="xtra">PMID:15296730</ref><references group="xtra"/>
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[[Category: Caspase-1]]
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[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Brien, T O.]]
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[[Category: Large Structures]]
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[[Category: McDowell, R S.]]
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[[Category: McDowell RS]]
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[[Category: Romanowski, M J.]]
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[[Category: O'Brien T]]
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[[Category: Scheer, J M.]]
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[[Category: Romanowski MJ]]
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[[Category: Ligand-free caspase-1]]
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[[Category: Scheer JM]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Feb 18 05:21:02 2009''
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Current revision

Crystal structure of an active-site ligand-free form of the human caspase-1 C285A mutant

PDB ID 1sc1

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