We study protein phenyl transferases, which are required for modification of proteins with farnesyl (C15) and geranylgeranyl (C20) groups. Prenylated proteins have important regulatory roles in processes such as cell division and differentiation. Our overall goals are to structurally characterize native and recombinant protein prenyl transferases from the malarial parasite, P. falciparum and establish the molecular basis for the binding of their substrates and inhibitors. Understanding the specificity and susceptibility of protein prenyl transferases to inhibition has great potential for aiding the development of anti-malarials. We have described a P. falciparum protein farnesyl transferase and shown that it is inhibited by selected peptidomimetics and that such inhibitions disrupts the P. falciparum life cycle. We also design, synthesize and test photolabile prenyl diphosphates as active site-directed probes. |
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Professor Emeritus