1MDW: Crystal Structure Of Calcium-bound Protease Core Of Calpain Ii Reveals The Basis For Intrinsic Inactivation

Uncontrolled activation of calpain can lead to necrotic cell death and irreversible tissue damage. We have discovered an intrinsic mechanism whereby the autolysis-generated protease core fragment of calpain is inactivated through the inherent instability of a key alpha-helix. This auto-inactivation state was captured by the 1.9 A Ca(2+)-bound structure of the protease core from m-calpain, and sequence alignments suggest that it applies to about half of the calpain isoforms. Intact calpain large subunits are also subject to this inhibition, which can be prevented through assembly of the heterodimers. Other isoforms or their released cores are not silenced by this mechanism and might contribute to calpain patho-physiologies.
PDB ID: 1MDWDownload
MMDB ID: 22617
PDB Deposition Date: 2002/8/7
Updated in MMDB: 2007/10
Experimental Method:
x-ray diffraction
Resolution: 1.95  Å
Source Organism:
Similar Structures:
Biological Unit for 1MDW: monomeric; determined by author
Molecular Components in 1MDW
Label Count Molecule
Protein (1 molecule)
Calpain II, Catalytic Subunit(Gene symbol: Capn2)
Molecule annotation
Chemicals (2 molecules)
* Click molecule labels to explore molecular sequence information.

Citing MMDB