Hookworm cathepsin D aspartic proteases: contributing roles in the host-specific degradation of serum proteins and skin macromolecules

Cathepsin D aspartic proteases of hookworms were recently implicated in the host-specific digestion of haemoglobin by adult parasites. Ac-APR-1 from the dog hookworm, Ancylostoma caninum and Na-APR-1 from the human hookworm, Necator americanus, were shown to be expressed in the infective larval stag...

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Bibliographic Details
Published in:Parasitology 2003-02, Vol.126 (2), p.179-185
Main Authors: WILLIAMSON, A. L., BRINDLEY, P. J., LOUKAS, A.
Format: Article
Language:English
Subjects:
albumin
Ancylostoma - enzymology
Ancylostoma - pathogenicity
Animals
Aspartic Acid Endopeptidases - chemistry
Aspartic Acid Endopeptidases - genetics
Aspartic Acid Endopeptidases - metabolism
aspartic protease
Biodegradation, Environmental
Biological and medical sciences
Blood Proteins - metabolism
Cathepsin D - chemistry
Cathepsin D - genetics
Cathepsin D - metabolism
collagen
Collagen - metabolism
Fibrinogen - metabolism
Fundamental and applied biological sciences. Psychology
haemoglobin
hookworm
Host parasite relation
pathogenicity
host specificity
Host-Parasite Interactions
Invertebrates
Necator americanus - enzymology
Necator americanus - pathogenicity
Nemathelminthia. Plathelmintha
Recombinant Proteins - metabolism
Skin - cytology
Skin - metabolism
Species Specificity
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Summary:Cathepsin D aspartic proteases of hookworms were recently implicated in the host-specific digestion of haemoglobin by adult parasites. Ac-APR-1 from the dog hookworm, Ancylostoma caninum and Na-APR-1 from the human hookworm, Necator americanus, were shown to be expressed in the infective larval stage (L3) as well as adult worms. We now show that both proteases degraded skin macromolecules and serum proteins, some of which were cleaved more readily from permissive definitive hosts as opposed to non-permissive hosts. Na-APR-1 degraded human collagens more efficiently than did Ac-APR-1, and Ac-APR-1 degraded canine serum albumin more efficiently than did Na-APR-1. On the other hand, both enzymes degraded human serum proteins (albumin and fibrinogen) with approximately equal efficiency under the conditions of our assays in vitro. Molecular models of these 2 orthologous, aspartic proteases showed that, despite having active site clefts with identical primary sequences, residues in the S3 pocket adopted different conformations, likely accounting for different substrate preferences reported previously. Antisera raised to both proteases partially inhibited (16–26%) migration of hookworm L3 through hamster skin in vitro, further implying a connective tissue invasive role for these enzymes in addition to digestion of serum and erythrocyte proteins for nutrition.
ISSN:0031-1820
1469-8161
DOI:10.1017/S0031182002002706