PYRROLIDONE CARBOXYL PEPTIDASE (PCP) - AN ENZYME THAT REMOVES PYROGLUTAMIC ACID (PGLU) FROM PGLU-PEPTIDES AND PGLU-PROTEINS

Pyrrolidone carboxyl peptidase (EC 3.4.11.8) is an exopeptidase common ly called PYRase, which hydrolytically removes the pGlu from pGlu-pept ides or pGlu-proteins. pGlu also known as pyrrolidone carboxylic - aci d may occur naturally by an enzymatic procedure or may occur as an art ifact in proteins or peptides. The enzymatic synthesis of pGlu suggest s that this residue may have important biological and physiological fu nctions. Several studies are consistent with this supposition. PYRase has been found in a variety of bacteria, and in plant, animal, and hum an tissues. For over two decades, biochemical and enzymatic properties of PYRase have been investigated At least two classes of PYRase have been characterized. The first one includes the bacterial and animal ty pe I PYRases and the second one the animal type II and serum PYRases. Enzymes from these two classes present differences in their molecular weight and in their enzymatic properties.Recently, the genes of PYRase s from four bacteria have been cloned and characterized, allowing the study of the primary structure of these enzymes, and their over-expres sion in heterologous organisms. Comparison of the primary structure of these enzymes revealed striking homologies. Type I PYRases and bacter ial PYRases are generally soluble enzymes, whereas type II PYRases are membrane-bound enzymes. PYRase II appears to play as important a phys iological role as other neuropeptide degrading enzymes. However, the r ole of type I and bacterial PYRases remains unclear. The primary appli cation of PYRase has been its utilization for some protein or peptide sequencing. Development of chromogenic substrates for this enzyme has allowed its use in bacterial diagnosis. (C) 1994 Wiley-Liss, Inc.