Bioinformatic Approach to Identify Penultimate Amino Acids Efficient for N-Terminal Methionine Excision

More than half of proteins in prokaryotes and eukaryotes undergo N-terminal methionine excision (NME). While it is known that the penultimate amino acid affects the efficiency of NME in several bacterial and eukaryotic species, it is experimentally difficult and tedious to verify which amino acid at the penultimate site (the site after initiator Met) is the most efficient for NME in different species. Here we present a new bioinformatic approach to identify penultimate amino acids that are efficient for NME. Amino acids most efficient for NME are alanine, serine and proline in human, and alanine, glycine, valine, proline and serine in the yeast Saccharomyces cerevisiae. This finding also helps resolve the two hypotheses that have been proposed to explain the presence of+4G site in the Kozak consensus for translation initiation.