1kfu

<table><tr><td colspan='2'>[[1kfu]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. 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>

</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1kfx|1kfx]]</div></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>

[[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. [[https://www.uniprot.org/uniprot/CPNS1_HUMAN CPNS1_HUMAN]] Regulatory subunit of the calcium-regulated non-lysosomal thiol-protease which catalyzes limited proteolysis of substrates involved in cytoskeletal remodeling and signal transduction.

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== Publication Abstract from PubMed ==

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.

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:10639123<ref>PMID:10639123</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>

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<div class="pdbe-citations 1kfu" style="background-color:#fffaf0;"></div>

== References ==

<references/>

[[Category: Calpain-2]]

[[Category: Human]]

[[Category: Bartunik, H]]

[[Category: Bode, W]]

[[Category: Bourenkow, G]]

[[Category: Braun, M]]

[[Category: Fernandez-Catalan, C]]

[[Category: Huber, R]]

[[Category: Irie, A]]

[[Category: Masumoto, H]]

[[Category: Nakagawa, K]]

[[Category: Sorimachi, H]]

[[Category: Strobl, S]]

[[Category: Suzuki, K]]

[[Category: Thiol-protease]]