This peptidase M20 subfamily includes CNDP1 (beta-Ala-His dipeptidase), CNDP2 (cytosolic nonspecific dipeptidase) and DUG1 from yeast, which are metallopeptidases [, ].Two genes, CN1 and CN2, that degrade carnosine (beta-alanyl-L-histidine) and homocarnosine (gamma-aminobutyric acid-L-histidine), two naturally occurring dipeptides with potential neuroprotective and neurotransmitter functions, have been identified. CN1 encodes for serum carnosinase and has narrow substrate specificity for Xaa-His dipeptides, where Xaa can be beta-alanine (carnosine), N-methyl beta-alanine, alanine, glycine and gamma-aminobutyric acid (homocarnosine). CN2 corresponds to the cytosolic nonspecific dipeptidase (CNDP2) and is not limited to Xaa-His dipeptides. CNDP2 requires Mn(2+) for full activity and does not hydrolyze homocarnosine [, , , , , ].Metallodipeptidase DUG1 is a subunit of the GSH degradosomal complex, involved in the degradation of glutathione (GSH) and other peptides containing a gamma-glu-X bond. Although dipeptides and tripeptides with a normal peptide bond, such as cys-gly or glu-cys-gly, can be hydrolysed by the DUG1 protein, the presence of an unusual peptide bond, such as in GSH, requires the participation of the DUG2 and DUG3 gene products as well. These three proteins form a GSH degradosomal complex [].
