An <em>in silico</em> mutagenesis effect on mode of action of curcin, a toxic protein from <em>Jatropha curcas</em>

Abstract

Curcin is a toxic protein found in the seeds of <em>Jatropha curcas</em> and belongs to the family of ribosome inactivating proteins (RIPs), which bind to the rRNA of ribosomes to inactivate them. Curcin is a type 2 RIP protein consisting of a single chain. Its presence makes it difficult to utilize the <em>Jatropha</em> seed cakes for animal feed. Inhibition of its biological activity against ribosomes through mutagenesis of protein structure is a novel and valid approach to understand its mode of action. Such mutations were introduced into the protein sequence and the protein was modeled to see their effect on interaction with GAGA loop of mouse 28S rRNA. Interestingly, with the removal or mutation of critical residues of the active site, the binding of curcin and rRNA molecule increased thus indicating towards the steric hindrance provided by these residues. The removal of these residues seems to increase the cavity size, thus, making it easier for the approaching rRNA molecule to bind closely. However, as all RIPs interact with rRNA by N-glycosidation action, the presence of amino acid (aa) residues may be crucial for providing chemical toxicity. This study paves way for a step ahead to see the effect of their removal or mutation in terms of N-glycosidase activity for better understanding.