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| | <StructureSection load='1zcm' size='340' side='right'caption='[[1zcm]], [[Resolution|resolution]] 2.00Å' scene=''> | | <StructureSection load='1zcm' size='340' side='right'caption='[[1zcm]], [[Resolution|resolution]] 2.00Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[1zcm]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1ZCM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1ZCM FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[1zcm]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1ZCM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1ZCM FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=C1N:N-[(BENZYLOXY)CARBONYL]LEUCYL-N~1~-[3-FLUORO-1-(4-HYDROXYBENZYL)-2-OXOPROPYL]LEUCINAMIDE'>C1N</scene>, <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]] 2Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CAPN1, CANPL1 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=C1N:N-[(BENZYLOXY)CARBONYL]LEUCYL-N~1~-[3-FLUORO-1-(4-HYDROXYBENZYL)-2-OXOPROPYL]LEUCINAMIDE'>C1N</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Calpain-1 Calpain-1], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.22.52 3.4.22.52] </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=1zcm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1zcm OCA], [https://pdbe.org/1zcm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1zcm RCSB], [https://www.ebi.ac.uk/pdbsum/1zcm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1zcm 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=1zcm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1zcm OCA], [https://pdbe.org/1zcm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1zcm RCSB], [https://www.ebi.ac.uk/pdbsum/1zcm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1zcm ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/CAN1_HUMAN CAN1_HUMAN]] Calcium-regulated non-lysosomal thiol-protease which catalyze limited proteolysis of substrates involved in cytoskeletal remodeling and signal transduction.
| + | [https://www.uniprot.org/uniprot/CAN1_HUMAN CAN1_HUMAN] 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: Calpain-1]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Human]]
| + | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Hanzlik, R P]] | + | [[Category: Hanzlik RP]] |
| - | [[Category: Li, Q]] | + | [[Category: Li Q]] |
| - | [[Category: Schonbrunn, E]] | + | [[Category: Schonbrunn E]] |
| - | [[Category: Weaver, R F]] | + | [[Category: Weaver RF]] |
| - | [[Category: Calcium binding]]
| + | |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Protease]]
| + | |
| - | [[Category: Thiol protease]]
| + | |
| Structural highlights
Function
CAN1_HUMAN 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
Calpain is a nearly ubiquitous Ca2+-activated proteolytic enzyme whose precise physiological function is unknown. However, aberrant Ca2+ homeostasis in the course of cellular injuries and certain diseases of the CNS appears to activate calpain, in turn promoting the degradation of key cytoskeletal and membrane proteins. Hyperactive calpain has also been implicated in various aging phenomena and diseases of late life. Therefore, calpain is considered a potential therapeutic target in preventing degenerations of many kinds. Despite its potential medicinal importance, known structural information about mu-calpain is limited to that from the rat enzyme. We have determined the crystal structure of the human mu-calpain protease core (hmuI-II) containing a Gly213Ala mutation and covalently inactivated by a peptidomimetic (ZLLYCH2F) at 2.0 A resolution. The methylene carbon of the inhibitor is bound to Cys115. Additional hydrogen bonding and hydrophobic interactions between active site residues and the inhibitor, including an intermolecular antiparallel beta-sheet arrangement characteristically observed with members of the papain family of cysteine proteinases, help to stabilize the complex and orient the inhibitor. The terminal ZL portion of the inhibitor is solvent-exposed and highly flexible, and is thus not involved in specific binding interactions with the enzyme. Two large enzyme regions flanking the active site are highly flexible; they may be important in recognition of calpain's natural protein substrates and in positioning them for catalysis. The implications for drug design are discussed.
Molecular mode of action of a covalently inhibiting peptidomimetic on the human calpain protease core.,Li Q, Hanzlik RP, Weaver RF, Schonbrunn E Biochemistry. 2006 Jan 24;45(3):701-8. PMID:16411745[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Li Q, Hanzlik RP, Weaver RF, Schonbrunn E. Molecular mode of action of a covalently inhibiting peptidomimetic on the human calpain protease core. Biochemistry. 2006 Jan 24;45(3):701-8. PMID:16411745 doi:http://dx.doi.org/10.1021/bi052077b
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