Structural highlights
Function
[CAN1_RAT] Calcium-regulated non-lysosomal thiol-protease which catalyze limited proteolysis of substrates involved in cytoskeletal remodeling and signal transduction.
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
The endogenous calpain inhibitor, calpastatin, modulates some patho-physiological aspects of calpain signaling. Excess calpain can escape this inhibition and as well, many calpain isoforms and autolytically generated protease core fragments are not inhibited by calpastatin. There is a need, therefore, to develop specific, cell-permeable calpain inhibitors to block uncontrolled proteolysis and prevent tissue damage during brain and heart ischemia, spinal-cord injury and Alzheimer's diseases. Here, we report the first high-resolution crystal structures of rat mu-calpain protease core complexed with two traditional, low molecular mass inhibitors, leupeptin and E64. These structures show that access to a slightly deeper, but otherwise papain-like active site is gated by two flexible loops. These loops are divergent among the calpain isoforms giving a potential structural basis for substrate/inhibitor selectivity over other papain-like cysteine proteases and between members of the calpain family.
Crystal structures of calpain-E64 and -leupeptin inhibitor complexes reveal mobile loops gating the active site.,Moldoveanu T, Campbell RL, Cuerrier D, Davies PL J Mol Biol. 2004 Nov 5;343(5):1313-26. PMID:15491615[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Moldoveanu T, Campbell RL, Cuerrier D, Davies PL. Crystal structures of calpain-E64 and -leupeptin inhibitor complexes reveal mobile loops gating the active site. J Mol Biol. 2004 Nov 5;343(5):1313-26. PMID:15491615 doi:10.1016/j.jmb.2004.09.016
