1tlo
From Proteopedia
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| - | [[Image:1tlo.jpg|left|200px]] | + | [[Image:1tlo.jpg|left|200px]] |
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| - | '''High resolution crystal structure of calpain I protease core in complex with E64''' | + | {{Structure |
| + | |PDB= 1tlo |SIZE=350|CAPTION= <scene name='initialview01'>1tlo</scene>, resolution 1.9Å | ||
| + | |SITE= | ||
| + | |LIGAND= <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene> and <scene name='pdbligand=E64:N-[N-[1-HYDROXYCARBOXYETHYL-CARBONYL]LEUCYLAMINO-BUTYL]-GUANIDINE'>E64</scene> | ||
| + | |ACTIVITY= [http://en.wikipedia.org/wiki/Calpain-1 Calpain-1], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.22.52 3.4.22.52] | ||
| + | |GENE= CAPN1, CLS1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10116 Rattus norvegicus]) | ||
| + | }} | ||
| + | |||
| + | '''High resolution crystal structure of calpain I protease core in complex with E64''' | ||
| + | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1TLO is a [ | + | 1TLO is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1TLO OCA]. |
==Reference== | ==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:[http:// | + | 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:[http://www.ncbi.nlm.nih.gov/pubmed/15491615 15491615] |
[[Category: Calpain-1]] | [[Category: Calpain-1]] | ||
[[Category: Rattus norvegicus]] | [[Category: Rattus norvegicus]] | ||
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[[Category: covalently-linked inhibitor at the active site (cysteine 115) forms a thioester]] | [[Category: covalently-linked inhibitor at the active site (cysteine 115) forms a thioester]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 14:20:05 2008'' |
Revision as of 12:20, 20 March 2008
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| , resolution 1.9Å | |||||||
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| Ligands: | and | ||||||
| Gene: | CAPN1, CLS1 (Rattus norvegicus) | ||||||
| Activity: | Calpain-1, with EC number 3.4.22.52 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
High resolution crystal structure of calpain I protease core in complex with E64
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
1TLO 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
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