Here we summarized what is known at the present about function, structure and effect of mutations in the human
prolidase. Among the
peptidases,
prolidase is the only metalloenzyme that cleaves the iminodipeptides containing a
proline or
hydroxyproline residue at the C-terminal end. It is relevant in the latest stage of
protein catabolism, particularly of those molecules rich in
imino acids such as
collagens, thus being involved in matrix remodelling. Beside its intracellular functions,
prolidase has an antitoxic effect against some organophosphorus molecules, can be used in dietary industry as bitterness
reducing agent and recently has been used as target
enzyme for specific
melanoma prodrug activation. Recombinant human
prolidase was produced in prokaryotic and eukaryotic hosts with biochemical properties similar to the endogenous
enzyme and represents a valid tool both to better understand the structure and
biological function of the
enzyme and to develop an
enzyme replacement therapy for the
prolidase deficiency (PD).
Prolidase deficiency is a rare recessive disorder caused by mutations in the
prolidase gene and characterized by severe skin lesions. Single amino acid substitutions, exon splicing, deletions and a duplication were described as causative for the disease and are mainly located at highly conserved
amino acids in the sequence of
prolidase from different species. The pathophysiology of PD is still poorly understood; we offer here a review of the molecular mechanisms so far hypothesized.