1kfu

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{{STRUCTURE_1kfu| PDB=1kfu | SCENE= }}
{{STRUCTURE_1kfu| PDB=1kfu | SCENE= }}
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'''Crystal Structure of Human m-Calpain Form II'''
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===Crystal Structure of Human m-Calpain Form II===
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==Overview==
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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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(as it appears on PubMed at http://www.pubmed.gov), where 10639123 is the PubMed ID number.
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{{ABSTRACT_PUBMED_10639123}}
==About this Structure==
==About this Structure==
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[[Category: Regulation]]
[[Category: Regulation]]
[[Category: Thiol-protease]]
[[Category: Thiol-protease]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 22:41:45 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jul 2 10:16:55 2008''

Revision as of 07:16, 2 July 2008

Template:STRUCTURE 1kfu

Crystal Structure of Human m-Calpain Form II

Template:ABSTRACT PUBMED 10639123

About this Structure

1KFU is a Protein complex structure of sequences from Homo sapiens. This structure supersedes the now removed PDB entry 1dkv. Full crystallographic information is available from OCA.

Reference

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

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