1kfu
From Proteopedia
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Crystal Structure of Human m-Calpain Form II
Overview
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.
About this Structure
1KFU is a Protein complex structure of sequences from Homo sapiens. This structure superseeds the now removed PDB entry 1DKV. Active as Hydrolase, with EC number and 3.4.22.53 3.4.22.52 and 3.4.22.53 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
Page seeded by OCA on Mon Nov 12 17:50:34 2007
