The homology modeling study of the bovine ì-calpain inhibitor-binding domains

Abstract Text: The activated mammalian CAPN-structures, the CAPN/CAST complex in particular, have become an invaluable target model using the structure-based virtual screening of drug candidates from discovery phase to development for over-activated CAPN. An important key to understanding CAPN1 inhibition by CAST is to determine at the molecular level how CAST interacts with CAPN1 to inhibit its protease activity. A 3D structure model of the bovine CAPN1/CAST4 complex was built by comparative modeling based on the only known rat CAPN2/CAST4 complex. The complex model suggests certain residues of the bovine CAST4, notably TIPPKYQ motif sequence, and the structural elements of these residues, which are important for CAPN1 inhibition. These functional interfaces will serve as to guide the site-mutagenesis to research the bovine CAPN1 structure-function relationships for the design of small molecules inhibitors to prevent uncontrolled and unspecific degradation in the proteolysis of key protease substrates.

Keywords:

bovine

μ-calpain

Calpastatin

Homology modeling