1KXR

Crystal Structure of Calcium-Bound Protease Core of Calpain I

Summary for 1KXR

• Entry DOI: 10.2210/pdb1kxr/pdb
• Related: 1AJ5 1ALW 1DF0 1DVI 1KFU 1KFX
• Descriptor: thiol protease DOMAINS I AND II, CALCIUM ION (3 entities in total)
• Functional Keywords: papain-related, calcium-dependent cysteine protease, two novel cooperative calcium sites, hydrolase
• Biological source: Rattus norvegicus (Norway rat)
• Cellular location: Cytoplasm (By similarity): P97571
• Total number of polymer chains: 2
• Total formula weight: 77737.29

Authors

Moldoveanu, T.,Hosfield, C.M.,Lim, D.,Elce, J.S.,Jia, Z.,Davies, P.L. (deposition date: 2002-02-01, release date: 2002-03-20, Last modification date: 2023-08-16)

Primary citation

Moldoveanu, T.,Hosfield, C.M.,Lim, D.,Elce, J.S.,Jia, Z.,Davies, P.L.
A Ca(2+) switch aligns the active site of calpain.
Cell(Cambridge,Mass.), 108:649-660, 2002

PubMed Abstract: Ca(2+) signaling by calpains leads to controlled proteolysis during processes ranging from cytoskeleton remodeling in mammals to sex determination in nematodes. Deregulated Ca(2+) levels result in aberrant proteolysis by calpains, which contributes to tissue damage in heart and brain ischemias as well as neurodegeneration in Alzheimer's disease. Here we show that activation of the protease core of mu calpain requires cooperative binding of two Ca(2+) atoms at two non-EF-hand sites revealed in the 2.1 A crystal structure. Conservation of the Ca(2+) binding residues defines an ancestral general mechanism of activation for most calpain isoforms, including some that lack EF-hand domains. The protease region is not affected by the endogenous inhibitor, calpastatin, and may contribute to calpain-mediated pathologies when the core is released by autoproteolysis.

PubMed: 11893336
DOI: 10.1016/S0092-8674(02)00659-1

Experimental method

X-RAY DIFFRACTION (2.07 Å)