Prolidase is a
metallopeptidase that is ubiquitous in nature and has been isolated from mammals, bacteria and archaea.
Prolidase specifically hydrolyzes
dipeptides with a prolyl residue in the carboxy terminus (NH(2)-X-/-Pro-COOH). Currently, the only solved structure of
prolidase is from the hyperthermophilic archaeon Pyrococcus furiosus. This
enzyme is of particular interest because it can be used in many biotechnological applications.
Prolidase is able to degrade toxic organophosphorus (OP) compounds, namely, by cleaving the P-F and P-O bonds in the
nerve agents,
sarin and
soman. Applications using
prolidase to detoxify OP
nerve agents include its incorporation into fire-fighting foams and as biosensors for OP compound detection. Prolidases are also employed in the cheese-ripening process to improve cheese taste and texture. In humans,
prolidase deficiency (PD) is a rare autosomal recessive disorder that affects the connective tissue. Symptoms of PD include skin lesions,
mental retardation and recurrent
respiratory infections.
Enzyme replacement therapies are currently being studied in an effort to optimize
enzyme delivery and stability for this application. Previously,
prolidase has been linked to
collagen metabolism and more recently is being associated with
melanoma. Increased
prolidase activity in
melanoma cell lines has lead investigators to create
cancer prodrugs targeting this
enzyme. Thus, there are many biotechnological applications using recombinant and native forms of
prolidase and this review will describe the biochemical and structural properties of prolidases as well as discuss their most current applications.