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| | <StructureSection load='3bow' size='340' side='right'caption='[[3bow]], [[Resolution|resolution]] 2.40Å' scene=''> | | <StructureSection load='3bow' size='340' side='right'caption='[[3bow]], [[Resolution|resolution]] 2.40Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3bow]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Buffalo_rat Buffalo rat]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3BOW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3BOW FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3bow]] is a 3 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=3BOW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3BOW FirstGlance]. <br> |
| - | </td></tr><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> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.4Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1df0|1df0]], [[1kfu|1kfu]], [[1kxr|1kxr]]</div></td></tr>
| + | <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> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Capn2 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10116 Buffalo rat]), Capns1, Capn4, Css1 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10116 Buffalo rat]), Cast ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10116 Buffalo rat])</td></tr> | + | |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Calpain-2 Calpain-2], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.22.53 3.4.22.53] </span></td></tr>
| + | |
| | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3bow FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3bow OCA], [https://pdbe.org/3bow PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3bow RCSB], [https://www.ebi.ac.uk/pdbsum/3bow PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3bow ProSAT]</span></td></tr> | | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3bow FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3bow OCA], [https://pdbe.org/3bow PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3bow RCSB], [https://www.ebi.ac.uk/pdbsum/3bow PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3bow ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[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. [[https://www.uniprot.org/uniprot/ICAL_RAT ICAL_RAT]] Specific inhibition of calpain (calcium-dependent cysteine protease). Plays a key role in postmortem tenderization of meat and have been proposed to be involved in muscle protein degradation in living tissue. [[https://www.uniprot.org/uniprot/CPNS1_RAT CPNS1_RAT]] Regulatory subunit of the calcium-regulated non-lysosomal thiol-protease which catalyzes limited proteolysis of substrates involved in cytoskeletal remodeling and signal transduction.
| + | [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. |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Buffalo rat]] | |
| - | [[Category: Calpain-2]] | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Campbell, R L]] | + | [[Category: Rattus norvegicus]] |
| - | [[Category: Davies, P L]] | + | [[Category: Campbell RL]] |
| - | [[Category: Hanna, R A]] | + | [[Category: Davies PL]] |
| - | [[Category: Cell membrane]] | + | [[Category: Hanna RA]] |
| - | [[Category: Cysteine protease]]
| + | |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Hydrolase-hydrolase inhibitor complex]]
| + | |
| - | [[Category: Inhibitor]]
| + | |
| - | [[Category: Membrane]]
| + | |
| - | [[Category: Phosphoprotein]]
| + | |
| - | [[Category: Protease]]
| + | |
| - | [[Category: Protease inhibitor]]
| + | |
| - | [[Category: Thiol protease]]
| + | |
| - | [[Category: Thiol protease inhibitor]]
| + | |
| Structural highlights
Function
CAN2_RAT Calcium-regulated non-lysosomal thiol-protease which catalyze limited proteolysis of substrates involved in cytoskeletal remodeling and signal transduction.
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Calpains are non-lysosomal calcium-dependent cysteine proteinases that selectively cleave proteins in response to calcium signals and thereby control cellular functions such as cytoskeletal remodelling, cell cycle progression, gene expression and apoptotic cell death. In mammals, the two best-characterized members of the calpain family, calpain 1 and calpain 2 (micro-calpain and m-calpain, respectively), are ubiquitously expressed. The activity of calpains is tightly controlled by the endogenous inhibitor calpastatin, which is an intrinsically unstructured protein capable of reversibly binding and inhibiting four molecules of calpain, but only in the presence of calcium. To date, the mechanism of inhibition by calpastatin and the basis for its absolute specificity have remained speculative. It was not clear how this unstructured protein inhibits calpains without being cleaved itself, nor was it known how calcium induced changes that facilitated the binding of calpastatin to calpain. Here we report the 2.4-A-resolution crystal structure of the calcium-bound calpain 2 heterodimer bound by one of the four inhibitory domains of calpastatin. Calpastatin is seen to inhibit calpain by occupying both sides of the active site cleft. Although the inhibitor passes through the active site cleft it escapes cleavage in a novel manner by looping out and around the active site cysteine. The inhibitory domain of calpastatin recognizes multiple lower affinity sites present only in the calcium-bound form of the enzyme, resulting in an interaction that is tight, specific and calcium dependent. This crystal structure, and that of a related complex, also reveal the conformational changes that calpain undergoes on binding calcium, which include opening of the active site cleft and movement of the domains relative to each other to produce a more compact enzyme.
Calcium-bound structure of calpain and its mechanism of inhibition by calpastatin.,Hanna RA, Campbell RL, Davies PL Nature. 2008 Nov 20;456(7220):409-12. PMID:19020623[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Hanna RA, Campbell RL, Davies PL. Calcium-bound structure of calpain and its mechanism of inhibition by calpastatin. Nature. 2008 Nov 20;456(7220):409-12. PMID:19020623 doi:10.1038/nature07451
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