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2r9c

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[[Image:2r9c.png|left|200px]]
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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 [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]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2R9C FirstGlance]. <br>
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</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><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><br>
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<tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2g8j|2g8j]], [[1kxr|1kxr]], [[1tl9|1tl9]], [[1tlo|1tlo]], [[2g8e|2g8e]], [[2r9f|2r9f]]</td></tr>
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<tr><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Capn1, Cls1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10116 Rattus norvegicus])</td></tr>
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<tr><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Calpain-1 Calpain-1], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.22.52 3.4.22.52] </span></td></tr>
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<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2r9c FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2r9c OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2r9c RCSB], [http://www.ebi.ac.uk/pdbsum/2r9c PDBsum]</span></td></tr>
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<table>
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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/chain_selection.php?pdb_ID=2ata 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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{{STRUCTURE_2r9c| PDB=2r9c | SCENE= }}
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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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===Calpain 1 proteolytic core inactivated by ZLAK-3001, an alpha-ketoamide===
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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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{{ABSTRACT_PUBMED_18702462}}
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==About this Structure==
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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==
*[[Calpain|Calpain]]
*[[Calpain|Calpain]]
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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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</StructureSection>
[[Category: Calpain-1]]
[[Category: Calpain-1]]
[[Category: Rattus norvegicus]]
[[Category: Rattus norvegicus]]

Revision as of 07:18, 29 September 2014

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

2r9c, resolution 1.80Å

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