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Abstract

Snake venom is a myriad of biologically active proteins and peptides. Three finger toxins are highly conserved in their molecular structure, but interestingly possess diverse biological functions. During the course of evolution the introduction of subtle mutations in loop regions and slight variations in the three dimensional structure, has resulted in their functional versatility. Cytotoxin-1(UniProt ID: P01467), isolated from Naja mossambica mossambica, showed the potential to inhibit chymotrypsin and the chymotryptic activity of the 20S proteasome. In the present work we describe a molec-ular model of cytotoxin-1 in complex with chymotrypsin, pre- pared by the online server ClusPro. Analysis of the molecular model shows that Cytotoxin-1(P01467) binds to chymotrypsin through its loop I located near the N -terminus. The concave side of loop I of the toxin fits well in the substrate binding pocket of the protease. We propose Phe" as the dedicated P1 site of the ligand. Being a potent inhibitor of the 20S proteasome, cytotoxin-1 (P01467) can serve as a potential antitumor agent. Already snake venom cytotoxins have been investigated for their ability as an anticancer agent. The molecular model of cytotoxin-1in complex with chymotrypsin provides important information towards understanding the complex formation.