Modeling of Inhibition Mechanism of Natural Ligands to Farnesyl Protein Transferase Using Molecular Docking

Abstract

Ras Proteins play important roles in the signal transduction necessary for the cell growth. In the tumour cells, approximately 30% of the Ras protein genes are mutated. 1 Ras proteins (H, N, and K) are small guanine nucleotide binding proteins that undergo a series of post-translational modifications including the farnesylation on the thiol group at the Ras C-terminus catalyzed by the farnesyl protein transferase (FPTase). 2 This is a mandatory process before anchoring to plasma membrane which is critical for its biological activity, e.g. cell proliferation and tumorigenesis. Recent work has demonstrated that specific inhibition of the FPTase might be interesting to find effective therapeutical agents for the treatment of cancer. 3 Many synthetic FPTase inhibitors have been tested including peptidomimetics in the past few years. However, a few examples of natural products inhibitors were reported. In a recent work, many natural ligands were isolated as possible inhibitors of FPTase. 4 In the course of their screening for protein inhibitors from herbal medicines, several