1nms

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[[Image:1nms.png|left|200px]]
 
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{{STRUCTURE_1nms| PDB=1nms | SCENE= }}
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==Caspase-3 tethered to irreversible inhibitor==
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<StructureSection load='1nms' size='340' side='right'caption='[[1nms]], [[Resolution|resolution]] 1.70&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[1nms]] 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=1NMS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1NMS 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]] 1.7&#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=161:5-[4-(1-CARBOXYMETHYL-2-OXO-PROPYLCARBAMOYL)-BENZYLSULFAMOYL]-2-HYDROXY-BENZOIC+ACID'>161</scene></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=1nms FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1nms OCA], [https://pdbe.org/1nms PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1nms RCSB], [https://www.ebi.ac.uk/pdbsum/1nms PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1nms ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/CASP3_HUMAN CASP3_HUMAN] Involved in the activation cascade of caspases responsible for apoptosis execution. At the onset of apoptosis it proteolytically cleaves poly(ADP-ribose) polymerase (PARP) at a '216-Asp-|-Gly-217' bond. Cleaves and activates sterol regulatory element binding proteins (SREBPs) between the basic helix-loop-helix leucine zipper domain and the membrane attachment domain. Cleaves and activates caspase-6, -7 and -9. Involved in the cleavage of huntingtin. Triggers cell adhesion in sympathetic neurons through RET cleavage.<ref>PMID:7596430</ref> <ref>PMID:21357690</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/nm/1nms_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.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=1nms 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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Cysteine aspartyl protease-3 (caspase-3) is a mediator of apoptosis and a therapeutic target for a wide range of diseases. Using a dynamic combinatorial technology, 'extended tethering', we identified unique nonpeptidic inhibitors for this enzyme. Extended tethering allowed the identification of ligands that bind to discrete regions of caspase-3 and also helped direct the assembly of these ligands into small-molecule inhibitors. We first designed a small-molecule 'extender' that irreversibly alkylates the cysteine residue of caspase-3 and also contains a thiol group. The modified protein was then screened against a library of disulfide-containing small-molecule fragments. Mass-spectrometry was used to identify ligands that bind noncovalently to the protein and that also form a disulfide linkage with the extender. Linking the selected fragments with binding elements from the extenders generates reversible, tight-binding molecules that are druglike and distinct from known inhibitors. One molecule derived from this approach inhibited apoptosis in cells.
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===Caspase-3 tethered to irreversible inhibitor===
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In situ assembly of enzyme inhibitors using extended tethering.,Erlanson DA, Lam JW, Wiesmann C, Luong TN, Simmons RL, DeLano WL, Choong IC, Burdett MT, Flanagan WM, Lee D, Gordon EM, O'Brien T Nat Biotechnol. 2003 Mar;21(3):308-14. Epub 2003 Feb 3. PMID:12563278<ref>PMID:12563278</ref>
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{{ABSTRACT_PUBMED_12563278}}
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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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==About this Structure==
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<div class="pdbe-citations 1nms" style="background-color:#fffaf0;"></div>
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[[1nms]] is a 2 chain structure of [[Caspase]] 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=1NMS OCA].
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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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==Reference==
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<references/>
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<ref group="xtra">PMID:012563278</ref><references group="xtra"/>
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__TOC__
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Brian, T O.]]
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[[Category: Large Structures]]
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[[Category: Choong, I C.]]
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[[Category: Choong IC]]
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[[Category: DeLano, W L.]]
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[[Category: DeLano WL]]
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[[Category: Erlanson, D A.]]
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[[Category: Erlanson DA]]
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[[Category: Flanagan, W M.]]
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[[Category: Flanagan WM]]
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[[Category: Lam, J.]]
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[[Category: Lam J]]
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[[Category: Lee, D.]]
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[[Category: Lee D]]
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[[Category: Luong, T N.]]
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[[Category: Luong TN]]
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[[Category: Simmons, R L.]]
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[[Category: O'Brian T]]
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[[Category: Wiesmann, C.]]
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[[Category: Simmons RL]]
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[[Category: Apoptosis]]
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[[Category: Wiesmann C]]
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[[Category: Caspase-3]]
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[[Category: Hydrolase]]
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[[Category: Inhibitor]]
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[[Category: Irreversible]]
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[[Category: Tether]]
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Current revision

Caspase-3 tethered to irreversible inhibitor

PDB ID 1nms

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