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1tlo
From Proteopedia
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|PDB= 1tlo |SIZE=350|CAPTION= <scene name='initialview01'>1tlo</scene>, resolution 1.9Å | |PDB= 1tlo |SIZE=350|CAPTION= <scene name='initialview01'>1tlo</scene>, resolution 1.9Å | ||
|SITE= | |SITE= | ||
| - | |LIGAND= <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene> | + | |LIGAND= <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <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] | + | |ACTIVITY= <span class='plainlinks'>[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] </span> |
|GENE= CAPN1, CLS1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10116 Rattus norvegicus]) | |GENE= CAPN1, CLS1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10116 Rattus norvegicus]) | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY=[[1kxr|1KXR]], [[1mdw|1MDW]], [[1dfo|1DFO]], [[1kfu|1KFU]], [[1kfx|1KFX]], [[1nx0|1NX0]], [[1tl9|1TL9]] | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1tlo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1tlo OCA], [http://www.ebi.ac.uk/pdbsum/1tlo PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1tlo RCSB]</span> | ||
}} | }} | ||
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[[Category: Davies, P L.]] | [[Category: Davies, P L.]] | ||
[[Category: Moldoveanu, T.]] | [[Category: Moldoveanu, T.]] | ||
| - | [[Category: CA]] | ||
| - | [[Category: E64]] | ||
[[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 | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 23:57:52 2008'' |
Revision as of 20:57, 30 March 2008
| |||||||
| , resolution 1.9Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , | ||||||
| Gene: | CAPN1, CLS1 (Rattus norvegicus) | ||||||
| Activity: | Calpain-1, with EC number 3.4.22.52 | ||||||
| Related: | 1KXR, 1MDW, 1DFO, 1KFU, 1KFX, 1NX0, 1TL9
| ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| 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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