Molecular Modeling of Cathepsin B protein in different Leishmania strains

Abstract

Cathepsin B like cysteine proteases representing a major component of the lysosomal proteolytic repertoire plays an important role in intracellular protein degradation. Comparative models of cathepsin B (CatB) protein of six different Leishmania strains were developed using MODELLER. The modeled three-dimensional (3-D) structure has the correct stereochemistry as gauged from the Ramachandran plot and good 3-D structure compatibility as assessed by PROCHECK and the DOPE score ( DS2.1, Accelrys ). T he modeled proteins were energy minimized and validated using standard dynamic cascade protocol (DS 2.1). Seven different disulfide bonding sites are predicted in CatB protein of Leishmania . Two domains were identified and different motifs are present in catB protein of Leishmania like aspargine glycosylation site, protein kinase phosphorylation site, Protein kinase C activation site, N-myristoylation site. Considering that cathepsin B is essential for survival of Leishmania , including for virulence to the mammalian host, it may be viewed as an attractive drug target.