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1kfu

From Proteopedia

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[[Image:1kfu.gif|left|200px]]<br /><applet load="1kfu" size="350" color="white" frame="true" align="right" spinBox="true"
 
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caption="1kfu, resolution 2.50&Aring;" />
 
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'''Crystal Structure of Human m-Calpain Form II'''<br />
 
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==Overview==
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==Crystal Structure of Human m-Calpain Form II==
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Calpains (calcium-dependent cytoplasmic cysteine proteinases) are implicated in processes such as cytoskeleton remodeling and signal transduction. The 2.3-A crystal structure of full-length heterodimeric [80-kDa (dI-dIV) + 30-kDa (dV+dVI)] human m-calpain crystallized in the absence of calcium reveals an oval disc-like shape, with the papain-like catalytic domain dII and the two calmodulin-like domains dIV+dVI occupying opposite poles, and the tumor necrosis factor alpha-like beta-sandwich domain dIII and the N-terminal segments dI+dV located between. Compared with papain, the two subdomains dIIa+dIIb of the catalytic unit are rotated against one another by 50 degrees, disrupting the active site and the substrate binding site, explaining the inactivity of calpains in the absence of calcium. Calcium binding to an extremely negatively charged loop of domain dIII (an electrostatic switch) could release the adjacent barrel-like subdomain dIIb to move toward the helical subdomain dIIa, allowing formation of a functional catalytic center. This switch loop could also mediate membrane binding, thereby explaining calpains' strongly reduced calcium requirements in vivo. The activity status at the catalytic center might be further modulated by calcium binding to the calmodulin domains via the N-terminal linkers.
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<StructureSection load='1kfu' size='340' side='right'caption='[[1kfu]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[1kfu]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=1dkv 1dkv]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1KFU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1KFU 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]] 2.5&#8491;</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=1kfu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1kfu OCA], [https://pdbe.org/1kfu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1kfu RCSB], [https://www.ebi.ac.uk/pdbsum/1kfu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1kfu ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/CAN2_HUMAN CAN2_HUMAN] 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/kf/1kfu_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=1kfu ConSurf].
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<div style="clear:both"></div>
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==About this Structure==
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==See Also==
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1KFU is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. This structure supersedes the now removed PDB entry 1DKV. Active as [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] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1KFU OCA].
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*[[Calpain 3D structures|Calpain 3D structures]]
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__TOC__
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==Reference==
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</StructureSection>
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The crystal structure of calcium-free human m-calpain suggests an electrostatic switch mechanism for activation by calcium., Strobl S, Fernandez-Catalan C, Braun M, Huber R, Masumoto H, Nakagawa K, Irie A, Sorimachi H, Bourenkow G, Bartunik H, Suzuki K, Bode W, Proc Natl Acad Sci U S A. 2000 Jan 18;97(2):588-92. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=10639123 10639123]
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[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Hydrolase]]
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[[Category: Large Structures]]
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[[Category: Protein complex]]
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[[Category: Bartunik H]]
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[[Category: Bartunik, H.]]
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[[Category: Bode W]]
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[[Category: Bode, W.]]
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[[Category: Bourenkow G]]
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[[Category: Bourenkow, G.]]
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[[Category: Braun M]]
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[[Category: Braun, M.]]
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[[Category: Fernandez-Catalan C]]
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[[Category: Fernandez-Catalan, C.]]
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[[Category: Huber R]]
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[[Category: Huber, R.]]
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[[Category: Irie A]]
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[[Category: Irie, A.]]
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[[Category: Masumoto H]]
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[[Category: Masumoto, H.]]
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[[Category: Nakagawa K]]
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[[Category: Nakagawa, K.]]
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[[Category: Sorimachi H]]
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[[Category: Sorimachi, H.]]
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[[Category: Strobl S]]
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[[Category: Strobl, S.]]
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[[Category: Suzuki K]]
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[[Category: Suzuki, K.]]
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[[Category: calcium]]
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[[Category: papain-like]]
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[[Category: regulation]]
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[[Category: thiol-protease]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:33:39 2008''
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Current revision

Crystal Structure of Human m-Calpain Form II

PDB ID 1kfu

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