1NX0

Structure of Calpain Domain 6 in Complex with Calpastatin DIC

Summary for 1NX0

• Entry DOI: 10.2210/pdb1nx0/pdb
• Related: 1NX1 1NX2 1NX3
• Descriptor: Calcium-dependent protease, small subunit, Calpastatin, Small molecule inhibitor, ... (5 entities in total)
• Functional Keywords: calcium binding, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• Biological source: Sus scrofa (pig); More
• Cellular location: Cytoplasm (By similarity): P04574
• Total number of polymer chains: 5
• Total formula weight: 42963.53

Authors

Todd, B.,Moore, D.,Deivanayagam, C.C.S.,Lin, G.-D.,Chattopadhyay, D.,Maki, M.,Wang, K.K.W.,Narayana, S.V.L. (deposition date: 2003-02-07, release date: 2003-08-19, Last modification date: 2024-02-14)

Primary citation

Todd, B.,Moore, D.,Deivanayagam, C.C.S.,Lin, G.-D.,Chattopadhyay, D.,Maki, M.,Wang, K.K.W.,Narayana, S.V.L.
A structural model for the inhibition of calpain by calpastatin: crystal structures of the native domain VI of calpain and its complexes with calpastatin peptide and a small molecule inhibitor.
J.Mol.Biol., 328:131-146, 2003

PubMed Abstract: The Ca(2+)-dependent cysteine protease calpain along with its endogenous inhibitor calpastatin is widely distributed. The interactions between calpain and calpastatin have been studied to better understand the nature of calpain inhibition by calpastatin, which can aid the design of small molecule inhibitors to calpain. Here we present the crystal structure of a complex between a calpastatin peptide and the calcium-binding domain VI of calpain. DIC19 is a 19 residue peptide, which corresponds to one of the three interacting domains of calpastatin, which is known to interact with domain VI of calpain. We present two crystal structures of DIC19 bound to domain VI of calpain, determined by molecular replacement methods to 2.5A and 2.2A resolution. In the process of crystallizing the inhibitor complex, a new native crystal form was identified which had the homodimer 2-fold axis along a crystallographic axis as opposed to the previously observed dimer in the asymmetric unit. The crystal structures of the native domain VI and its inhibitor PD150606 (3-(4-iodophenyl)-2-mercapto-(Z)-2-propenoic acid) complex were determined with the help of molecular replacement methods to 2.0A and 2.3A resolution, respectively. In addition, we built a homology model for the complex between domain IV and DIA19 peptide of calpastatin. Finally, we present a model for the calpastatin-inhibited calpain.

PubMed: 12684003
DOI: 10.1016/S0022-2836(03)00274-2

Experimental method

X-RAY DIFFRACTION (2.3 Å)