1TLO
High resolution crystal structure of calpain I protease core in complex with E64
Summary for 1TLO
| Entry DOI | 10.2210/pdb1tlo/pdb |
| Related | 1DFO 1KFU 1KFX 1KXR 1MDW 1NX0 1TL9 |
| Descriptor | Calpain 1, large [catalytic] subunit, CALCIUM ION, N-[N-[1-HYDROXYCARBOXYETHYL-CARBONYL]LEUCYLAMINO-BUTYL]-GUANIDINE, ... (4 entities in total) |
| Functional Keywords | covalently-linked inhibitor at the active site (cysteine 115) forms a thioester, hydrolase |
| Biological source | Rattus norvegicus (Norway rat) |
| Cellular location | Cytoplasm : P97571 |
| Total number of polymer chains | 1 |
| Total formula weight | 39245.14 |
| Authors | Moldoveanu, T.,Campbell, R.L.,Cuerrier, D.,Davies, P.L. (deposition date: 2004-06-09, release date: 2004-11-02, Last modification date: 2024-11-13) |
| Primary citation | Moldoveanu, T.,Campbell, R.L.,Cuerrier, D.,Davies, P.L. Crystal Structures of Calpain-E64 and -Leupeptin Inhibitor Complexes Reveal Mobile Loops Gating the Active Site J.Mol.Biol., 343:1313-1326, 2004 Cited by PubMed Abstract: 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. PubMed: 15491615DOI: 10.1016/j.jmb.2004.09.016 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.9 Å) |
Structure validation
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