1tl9
From Proteopedia
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High resolution crystal structure of calpain I protease core in complex with leupeptin
Overview
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.
About this Structure
1TL9 is a Single protein structure of sequence from Rattus norvegicus with CA and ACE as ligands. Active as Calpain-1, with EC number 3.4.22.52 Full crystallographic information is available from OCA.
Reference
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
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