Structure of N-myristoyltransferase with bound myristoylCoA and peptide substrate analogs

N-myristoyltransferase (Nmt) attaches myristate to the N-terminal glycine o f many important eukaryotic and viral proteins. It is a target for anti-fun gal and anti-viral therapy. We have determined the structure, to 2.9 Angstr om resolution, of a ternary complex of Saccharomyces cerevisiae Nmt1p with bound myristoylCoA and peptide substrate analogs. The model reveals structu ral features that define the enzyme's substrate specificities and regulate the ordered binding and release of substrates and products. A novel catalyt ic mechanism is proposed involving deprotonation of the N-terminal ammonium of a peptide substrate by the enzyme's C-terminal backbone carboxylate.