2r9c

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[[Image:2r9c.png|left|200px]]
 
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{{STRUCTURE_2r9c| PDB=2r9c | SCENE= }}
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==Calpain 1 proteolytic core inactivated by ZLAK-3001, an alpha-ketoamide==
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<StructureSection load='2r9c' size='340' side='right'caption='[[2r9c]], [[Resolution|resolution]] 1.80&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[2r9c]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2R9C OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2R9C 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]] 1.8&#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=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=GRD:BENZYL+(S)-1-((2S,3S)-1-(3-(6-AMINO-9H-PURIN-9-YL)PROPYLAMINO)-2-HYDROXY-1-OXOPENTAN-3-YLAMINO)-4-METHYL-1-OXOPENTAN-2-YLCARBAMATE'>GRD</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=2r9c FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2r9c OCA], [https://pdbe.org/2r9c PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2r9c RCSB], [https://www.ebi.ac.uk/pdbsum/2r9c PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2r9c ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/CAN1_RAT CAN1_RAT] Calcium-regulated non-lysosomal thiol-protease which catalyze limited proteolysis of substrates involved in cytoskeletal remodeling and signal transduction.
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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/r9/2r9c_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=2r9c 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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Calpains are intracellular cysteine proteases that catalyze the cleavage of target proteins in response to Ca(2+) signaling. When Ca(2+) homeostasis is disrupted, calpain overactivation causes unregulated proteolysis, which can contribute to diseases such as postischemic injury and cataract formation. Potent calpain inhibitors exist, but of these many cross-react with other cysteine proteases and will need modification to specifically target calpain. Here, we present crystal structures of rat calpain 1 protease core (muI-II) bound to two alpha-ketoamide-based calpain inhibitors containing adenyl and piperazyl primed-side extensions. An unexpected aromatic-stacking interaction is observed between the primed-side adenine moiety and the Trp298 side chain. This interaction increased the potency of the inhibitor toward muI-II and heterodimeric m-calpain. Moreover, stacking orients the adenine such that it can be used as a scaffold for designing novel primed-side address regions, which could be incorporated into future inhibitors to enhance their calpain specificity.
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===Calpain 1 proteolytic core inactivated by ZLAK-3001, an alpha-ketoamide===
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Cocrystal structures of primed side-extending alpha-ketoamide inhibitors reveal novel calpain-inhibitor aromatic interactions.,Qian J, Cuerrier D, Davies PL, Li Z, Powers JC, Campbell RL J Med Chem. 2008 Sep 11;51(17):5264-70. Epub 2008 Aug 15. PMID:18702462<ref>PMID:18702462</ref>
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{{ABSTRACT_PUBMED_18702462}}
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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 2r9c" style="background-color:#fffaf0;"></div>
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[[2r9c]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2R9C OCA].
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==See Also==
==See Also==
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*[[Calpain|Calpain]]
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*[[Calpain 3D structures|Calpain 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:018702462</ref><references group="xtra"/>
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__TOC__
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[[Category: Calpain-1]]
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</StructureSection>
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[[Category: Large Structures]]
[[Category: Rattus norvegicus]]
[[Category: Rattus norvegicus]]
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[[Category: Campbell, R L.]]
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[[Category: Campbell RL]]
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[[Category: Davies, P L.]]
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[[Category: Davies PL]]
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[[Category: Qian, J.]]
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[[Category: Qian J]]
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[[Category: Alpha-ketoamide]]
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[[Category: Hydrolase]]
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[[Category: Inhibitor]]
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[[Category: Membrane]]
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[[Category: Peptidase]]
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[[Category: Protease]]
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[[Category: Thiol protease]]
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Current revision

Calpain 1 proteolytic core inactivated by ZLAK-3001, an alpha-ketoamide

PDB ID 2r9c

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Proteopedia Page Contributors and Editors (what is this?)

OCA

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