Aminopeptidases

Abstract

Aminopeptidases hydrolyse peptide bonds at the N-terminus of proteins and polypeptides whereas carboxypeptidases hydrolyse peptide bonds at the C-terminus. Omega peptidase is an additional term referring to special types of aminopeptidases and carboxypeptidases that are capable of removing terminal residues lacking a free α-amino or α-carboxyl group, or include linkages other than the α-peptide type (e.g. pyroglutamyl peptidases; McDonald and Barret, 1986). Aminopeptidases can be subdivided into three groups: aminopeptidases in the strict sense which hydrolyse the first peptide bond in a polypeptide chain with the release of a single amino acid residue (aminoacyl- and iminoacyl peptidases [EC 3.4.11]); those that remove dipeptides or tripeptides (dipeptidyl- and tripeptidyl peptidases [EC 3.4.14]) from polypeptide chains; and those which only hydrolyse di- or tripeptides (dipeptidases [EC 3.4.15] and tripeptidases [EC 3.4.14.4]) (Sanderink et al., 1988). Aminopeptidases are widely distributed among bacteria, fungi, plants and mammals (Gonzales and Robert-Baudouy, 1996; Sanz et al., 2002; Tu et al., 2003; Barret et al., 2004). Theses enzymes are located in different subcellular compartments including the cytoplasm, lysosomes and membranes, and can also be secreted into the extracellular medium. Based on catalytic mechanism, most of the aminopeptidases are metallo-enzymes but cysteine and serine peptidases are also included in this group. Though some aminopeptidases are monomeric, most show multimeric structures particularly those from eukaryotic organisms (McDonald and Barret, 1986; Jones, 1991; Lowther and Matthews, 2002). The three-dimensional structures of some aminopeptidases have been solved, contributing to the understanding of their catalytic mechanism and functions (Kim et al., 1993; Bazan et al., 1994; Joshua-Tor et al., 1995; Lowther and Matthews, 2002). Aminopeptidases appear to act in concert with other peptidases to complete diverse proteolytic pathways. Thus, these enzymes can efficiently retrieve amino acids from dietary proteins and endogenous proteins degraded during protein turnover, thereby covering nutritional as well as other biological roles including protein maturation, hormone level regulation and cell-cycle control (McDonald and Barret, 1986; Christensen et al., 1999). Many of the mammalian enzymes play important functions in cellular processes involved in health and disease and, as a consequence, constitute targets for the pharmaceutical industry (Scornik and Botbol, 2001; Holz et al., 2003; Rigolet et al., 2005; Inguimbert et al., 2005). Some aminopeptidases are also of great interest for their biotechnological and agro-industrial applications (Seppo et al., 2003; FitzGerald and OCuinn, 2006). © 2007 Springer.