Characterization of N-myristoyltransferase from Plasmodium falciparum

The gene coding for myristoyl-CoA:protein N-myristoyltransferase (NMT) has been cloned from the malaria parasite Plasmodium falciparum. The gene appea rs to be single copy and mRNA is expressed in asexual blood-stage forms. Co mparison of cDNA and genomic sequences identified three small introns. The open reading frame codes for a 410-amino-acid protein and no evidence of fo rms with an extended N-terminal coding sequence was obtained. Residues impo rtant in substrate binding and in the catalytic mechanism in other species are conserved. The protein was expressed from a plasmid in Escherichia coli , partially purified and shown to have enzymic activity using a synthetic p eptide substrate. Comparison of the malaria parasite protein with that deri ved from the human gene showed a different pattern of inhibition by chemica l modification. Human NMT activity was inhibited by diethylpyrocarbonate an d partially inhibited by iodacetamide, whereas P. falciparum NMT activity w as not inhibited by either pre-treatment. Since the enzyme in infectious fu ngi is a target for potential chemotherapeutic drugs, it should also be inv estigated in the context of parasitic infections such as that responsible f or malaria.