Aminopeptidases

Abstract

Aminopeptidases are proteolytic enzymes that remove L-amino acids sequentially from the amino termini of polypeptide chains. A number of aminopeptidases have been isolated, including leucine aminopeptidase from serine kidney cytosol (1), aminopeptidase P from E. coli (2), proline iminopeptidase from E. coli, and swine kidney (3), aminopeptidase B from rat liver (4), and aminopeptidase A from rat kidney (5). However, three aminopeptidases in particular have found routine use in protein chemistry. The first is pyroglutamate aminopeptidase, a thiol exoprotease that cleaves N-terminal pyroglutamyl residues (pyrrolidone carboxylic acid) from peptides and proteins (6–10). N-terminal glutamine residues can readily cyclize to the pyroglutamyl derivative (Fig. 1). This can occur during peptide and protein purification (it is uncertain whether the N-terminal pyroglutamyl residues of a number of naturally occurring peptides and proteins are genuine posttranslational modifications, or were introduced by cyclization of N-terminal glutamine during purification) or during sequence determination when glutamine was the newly liberated N-terminal amino acid. This cyclized derivative does not have a free amino group, and therefore, the peptide or protein is not amenable to sequence determination, unless the pyroglutamyl derivative is removed by pyroglutamate aminopeptrdase (11,12).