2c2m

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[[Image:2c2m.png|left|200px]]
 
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==Crystal structures of caspase-3 in complex with aza-peptide Michael acceptor inhibitors.==
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The line below this paragraph, containing "STRUCTURE_2c2m", creates the "Structure Box" on the page.
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<StructureSection load='2c2m' size='340' side='right'caption='[[2c2m]], [[Resolution|resolution]] 1.94&Aring;' scene=''>
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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'>[[2c2m]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2C2M OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2C2M 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]] 1.94&#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=MX4:{1-[4-(BENZYLOXY)-4-OXOBUTANOYL]HYDRAZINO}ACETIC+ACID'>MX4</scene>, <scene name='pdbligand=PHQ:BENZYL+CHLOROCARBONATE'>PHQ</scene></td></tr>
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{{STRUCTURE_2c2m| PDB=2c2m | 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=2c2m FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2c2m OCA], [https://pdbe.org/2c2m PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2c2m RCSB], [https://www.ebi.ac.uk/pdbsum/2c2m PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2c2m 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/c2/2c2m_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=2c2m 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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Aza-peptide Michael acceptors are a novel class of inhibitors that are potent and specific for caspases-2, -3, -6, -7, -8, -9, and -10. The second-order rate constants are in the order of 10(6) M(-1) s(-1). The aza-peptide Michael acceptor inhibitor 18t (Cbz-Asp-Glu-Val-AAsp-trans-CH=CH-CON(CH(2)-1-Naphth)(2) is the most potent compound and it inhibits caspase-3 with a k(2) value of 5620000 M(-1) s(-1). The inhibitor 18t is 13700, 190, 6.4, 594, 37500, and 173-fold more selective for caspase-3 over caspases-2, -6, -7, -8, -9, and -10, respectively. Aza-peptide Michael acceptors designed with caspase specific sequences are selective and do not show any cross reactivity with clan CA cysteine proteases such as papain, cathepsin B, and calpains. High-resolution crystal structures of caspase-3 and caspase-8 in complex with aza-peptide Michael acceptor inhibitors demonstrate the nucleophilic attack on C2 and provide insight into the selectivity and potency of the inhibitors with respect to the P1' moiety.
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===CRYSTAL STRUCTURES OF CASPASE-3 IN COMPLEX WITH AZA-PEPTIDE MICHAEL ACCEPTOR INHIBITORS.===
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Design, synthesis, and evaluation of aza-peptide Michael acceptors as selective and potent inhibitors of caspases-2, -3, -6, -7, -8, -9, and -10.,Ekici OD, Li ZZ, Campbell AJ, James KE, Asgian JL, Mikolajczyk J, Salvesen GS, Ganesan R, Jelakovic S, Grutter MG, Powers JC J Med Chem. 2006 Sep 21;49(19):5728-49. PMID:16970398<ref>PMID:16970398</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 class="pdbe-citations 2c2m" style="background-color:#fffaf0;"></div>
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(as it appears on PubMed at http://www.pubmed.gov), where 16970398 is the PubMed ID number.
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{{ABSTRACT_PUBMED_16970398}}
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==About this Structure==
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[[2c2m]] is a 3 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=2C2M OCA].
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==See Also==
==See Also==
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*[[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:016970398</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: Asgian, J L.]]
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[[Category: Large Structures]]
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[[Category: Campbell, A J.]]
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[[Category: Synthetic construct]]
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[[Category: Ekici, O D.]]
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[[Category: Asgian JL]]
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[[Category: Ganesan, R.]]
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[[Category: Campbell A]]
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[[Category: Gruetter, M G.]]
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[[Category: Ekici OD]]
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[[Category: James, K E.]]
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[[Category: Ganesan R]]
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[[Category: Jelakovic, S.]]
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[[Category: Gruetter MG]]
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[[Category: Li, Z Z.]]
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[[Category: James KE]]
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[[Category: Mikolajczyk, J.]]
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[[Category: Jelakovic S]]
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[[Category: Powers, J C.]]
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[[Category: Li ZZ]]
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[[Category: Salvesen, G S.]]
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[[Category: Mikolajczyk J]]
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[[Category: Apoptosis]]
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[[Category: Powers JC]]
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[[Category: Aza-asp]]
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[[Category: Salvesen GS]]
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[[Category: Aza-peptide]]
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[[Category: Clan cd]]
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[[Category: Cpp32]]
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[[Category: Cysteine-protease]]
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[[Category: Hydrolase-hydrolase inhibitor complex]]
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[[Category: Ice]]
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[[Category: Michael acceptor]]
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[[Category: Thiol protease]]
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[[Category: Yama]]
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[[Category: Zymogen]]
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Current revision

Crystal structures of caspase-3 in complex with aza-peptide Michael acceptor inhibitors.

PDB ID 2c2m

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