2p2c

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[[Image:2p2c.gif|left|200px]]
 
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{{Structure
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==Inhibition of caspase-2 by a designed ankyrin repeat protein (DARPin)==
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|PDB= 2p2c |SIZE=350|CAPTION= <scene name='initialview01'>2p2c</scene>, resolution 3.24&Aring;
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<StructureSection load='2p2c' size='340' side='right'caption='[[2p2c]], [[Resolution|resolution]] 3.24&Aring;' scene=''>
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|SITE=
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== Structural highlights ==
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|LIGAND=
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<table><tr><td colspan='2'>[[2p2c]] is a 18 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=2P2C OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2P2C FirstGlance]. <br>
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|ACTIVITY=
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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]] 3.24&#8491;</td></tr>
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|GENE= CASP2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])
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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=2p2c FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2p2c OCA], [https://pdbe.org/2p2c PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2p2c RCSB], [https://www.ebi.ac.uk/pdbsum/2p2c PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2p2c ProSAT]</span></td></tr>
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|DOMAIN=
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</table>
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|RELATEDENTRY=[[1pyo|1PYO]], [[1mjo|1MJO]]
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== Function ==
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|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2p2c FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2p2c OCA], [http://www.ebi.ac.uk/pdbsum/2p2c PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2p2c RCSB]</span>
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[https://www.uniprot.org/uniprot/CASP2_HUMAN CASP2_HUMAN] Involved in the activation cascade of caspases responsible for apoptosis execution. Might function by either activating some proteins required for cell death or inactivating proteins necessary for cell survival.
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}}
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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/p2/2p2c_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=2p2c 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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Specific and potent caspase inhibitors are indispensable for the dissection of the intricate pathways leading to apoptosis. We selected a designed ankyrin repeat protein (DARPin) from a combinatorial library that inhibits caspase-2 in vitro with a subnanomolar inhibition constant and, in contrast to the peptidic caspase inhibitors, with very high specificity for this particular caspase. The crystal structure of this inhibitor (AR_F8) in complex with caspase-2 reveals the molecular basis for the specificity and, together with kinetic analyses, the allosteric mechanism of inhibition. The structure also shows a conformation of the active site that can be exploited for the design of inhibitory compounds. AR_F8 is a specific inhibitor of an initiator caspase and has the potential to help identify the function of caspase-2 in the complex biological apoptotic signaling network.
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'''Inhibition of caspase-2 by a designed ankyrin repeat protein (DARPin)'''
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Inhibition of caspase-2 by a designed ankyrin repeat protein: specificity, structure, and inhibition mechanism.,Schweizer A, Roschitzki-Voser H, Amstutz P, Briand C, Gulotti-Georgieva M, Prenosil E, Binz HK, Capitani G, Baici A, Pluckthun A, Grutter MG Structure. 2007 May;15(5):625-36. PMID:17502107<ref>PMID:17502107</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 2p2c" style="background-color:#fffaf0;"></div>
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==Overview==
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==See Also==
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Specific and potent caspase inhibitors are indispensable for the dissection of the intricate pathways leading to apoptosis. We selected a designed ankyrin repeat protein (DARPin) from a combinatorial library that inhibits caspase-2 in vitro with a subnanomolar inhibition constant and, in contrast to the peptidic caspase inhibitors, with very high specificity for this particular caspase. The crystal structure of this inhibitor (AR_F8) in complex with caspase-2 reveals the molecular basis for the specificity and, together with kinetic analyses, the allosteric mechanism of inhibition. The structure also shows a conformation of the active site that can be exploited for the design of inhibitory compounds. AR_F8 is a specific inhibitor of an initiator caspase and has the potential to help identify the function of caspase-2 in the complex biological apoptotic signaling network.
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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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2P2C 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=2P2C OCA].
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__TOC__
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</StructureSection>
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==Reference==
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Inhibition of caspase-2 by a designed ankyrin repeat protein: specificity, structure, and inhibition mechanism., Schweizer A, Roschitzki-Voser H, Amstutz P, Briand C, Gulotti-Georgieva M, Prenosil E, Binz HK, Capitani G, Baici A, Pluckthun A, Grutter MG, Structure. 2007 May;15(5):625-36. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/17502107 17502107]
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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: Briand, C.]]
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[[Category: Briand C]]
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[[Category: Capitani, G.]]
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[[Category: Capitani G]]
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[[Category: Gruetter, M G.]]
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[[Category: Gruetter MG]]
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[[Category: Voser, HRoschitzki.]]
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[[Category: Roschitzki Voser H]]
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[[Category: apoptosis]]
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[[Category: caspase]]
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[[Category: caspase-2]]
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[[Category: designed ankyrin repeat protein]]
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[[Category: inhibition]]
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[[Category: protein design]]
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[[Category: protein library]]
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[[Category: ribosome display]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 04:27:35 2008''
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Current revision

Inhibition of caspase-2 by a designed ankyrin repeat protein (DARPin)

PDB ID 2p2c

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