1tl9: Difference between revisions
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'''High resolution crystal structure of calpain I protease core in complex with leupeptin''' | {{Structure | ||
|PDB= 1tl9 |SIZE=350|CAPTION= <scene name='initialview01'>1tl9</scene>, resolution 1.80Å | |||
|SITE= | |||
|LIGAND= <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene> and <scene name='pdbligand=ACE:ACETYL GROUP'>ACE</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 leupeptin''' | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
1TL9 is a [ | 1TL9 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=1TL9 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 forms a hemithioacetal]] | [[Category: covalently-linked inhibitor at the active site cysteine forms a hemithioacetal]] | ||
''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 14:19:53 2008'' | ||
Revision as of 12:19, 20 March 2008
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| 1tl9, resolution 1.80Å | |||||||||||||
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| Ligands: | CA and ACE | ||||||||||||
| 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 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
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