1mdw

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[[Image:1mdw.gif|left|200px]]
 
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{{Structure
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==Crystal Structure of Calcium-Bound Protease Core of Calpain II Reveals the Basis for Intrinsic Inactivation==
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|PDB= 1mdw |SIZE=350|CAPTION= <scene name='initialview01'>1mdw</scene>, resolution 1.95&Aring;
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<StructureSection load='1mdw' size='340' side='right'caption='[[1mdw]], [[Resolution|resolution]] 1.95&Aring;' scene=''>
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|SITE=
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== Structural highlights ==
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|LIGAND= <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>
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<table><tr><td colspan='2'>[[1mdw]] is a 2 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=1MDW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1MDW FirstGlance]. <br>
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|ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/Hydrolase Hydrolase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.22.52 and 3.4.22.53 3.4.22.52 and 3.4.22.53] </span>
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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]] 1.95&#8491;</td></tr>
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|GENE= CALPAIN II ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10116 Rattus norvegicus])
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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></td></tr>
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|DOMAIN=
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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=1mdw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1mdw OCA], [https://pdbe.org/1mdw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1mdw RCSB], [https://www.ebi.ac.uk/pdbsum/1mdw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1mdw ProSAT]</span></td></tr>
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|RELATEDENTRY=[[1kxr|1KXR]], [[1kfu|1KFU]], [[1kfx|1KFX]], [[1dfo|1DFO]], [[1aj5|1AJ5]], [[1alw|1ALW]]
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</table>
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|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1mdw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1mdw OCA], [http://www.ebi.ac.uk/pdbsum/1mdw PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1mdw RCSB]</span>
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== Function ==
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}}
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[https://www.uniprot.org/uniprot/CAN2_RAT CAN2_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/md/1mdw_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=1mdw ConSurf].
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<div style="clear:both"></div>
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'''Crystal Structure of Calcium-Bound Protease Core of Calpain II Reveals the Basis for Intrinsic Inactivation'''
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==See Also==
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*[[Calpain 3D structures|Calpain 3D structures]]
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__TOC__
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==Overview==
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</StructureSection>
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Uncontrolled activation of calpain can lead to necrotic cell death and irreversible tissue damage. We have discovered an intrinsic mechanism whereby the autolysis-generated protease core fragment of calpain is inactivated through the inherent instability of a key alpha-helix. This auto-inactivation state was captured by the 1.9 A Ca(2+)-bound structure of the protease core from m-calpain, and sequence alignments suggest that it applies to about half of the calpain isoforms. Intact calpain large subunits are also subject to this inhibition, which can be prevented through assembly of the heterodimers. Other isoforms or their released cores are not silenced by this mechanism and might contribute to calpain patho-physiologies.
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[[Category: Large Structures]]
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==About this Structure==
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1MDW is a [[Single protein]] structure of 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=1MDW OCA].
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==Reference==
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Calpain silencing by a reversible intrinsic mechanism., Moldoveanu T, Hosfield CM, Lim D, Jia Z, Davies PL, Nat Struct Biol. 2003 May;10(5):371-8. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/12665854 12665854]
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[[Category: Hydrolase]]
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[[Category: Rattus norvegicus]]
[[Category: Rattus norvegicus]]
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[[Category: Single protein]]
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[[Category: Davies PL]]
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[[Category: Davies, P L.]]
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[[Category: Hosfield CM]]
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[[Category: Hosfield, C M.]]
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[[Category: Jia Z]]
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[[Category: Jia, Z.]]
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[[Category: Lim D]]
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[[Category: Lim, D.]]
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[[Category: Moldoveanu T]]
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[[Category: Moldoveanu, T.]]
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[[Category: calpain cysteine protease fold]]
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[[Category: helix instability]]
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[[Category: tryptophan-based active site blockage]]
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[[Category: two cooperative calcium site]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 22:14:51 2008''
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Current revision

Crystal Structure of Calcium-Bound Protease Core of Calpain II Reveals the Basis for Intrinsic Inactivation

PDB ID 1mdw

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