1tl9
From Proteopedia
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'''High resolution crystal structure of calpain I protease core in complex with leupeptin''' | '''High resolution crystal structure of calpain I protease core in complex with leupeptin''' | ||
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[[Category: Davies, P L.]] | [[Category: Davies, P L.]] | ||
[[Category: Moldoveanu, T.]] | [[Category: Moldoveanu, T.]] | ||
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Revision as of 07:05, 3 May 2008
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. 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 Page seeded by OCA on Sat May 3 10:05:20 2008
