Human prolidase and prolidase deficiency: an overview on the characterization of the enzyme involved in proline recycling and on the effects of its mutations |
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Authors: | A Lupi R Tenni A Rossi G Cetta A Forlino |
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Institution: | (1) Department of Biochemistry, Section of Medicine and Pharmacy, University of Pavia, Via Taramelli 3/B, 27100 Pavia, Italy; |
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Abstract: | 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. |
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