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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
A multienzyme network functions in intestinal protein digestion by a platyhelminth parasite
Journal of Biological Chemistry, Volume 281, No. 51, Year 2006
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Description
Proteases frequently function not only as individual enzymes but also in cascades or networks. A notable evolutionary switch occurred in one such protease network that is involved in protein digestion in the intestine. In vertebrates, this is largely the work of trypsin family serine proteases, whereas in invertebrates, cysteine proteases of the papain family and aspartic proteases assume the role. Utilizing a combination of protease class-specific inhibitors and RNA interference, we deconvoluted such a network of major endopeptidases functioning in invertebrate intestinal protein digestion, using the parasitic helminth, Schistosoma mansoni as an experimental model. We show that initial degradation of host blood proteins is ordered, occasionally redundant, and substrate-specific. Although inhibition of parasite cathepsin D had a greater effect on primary cleavage of hemoglobin, inhibition of cathepsin B predominated in albumin degradation. Nevertheless, in both cases, inhibitor combinations were synergistic. An asparaginyl endopeptidase (legumain) also synergized with cathepsin B and L in protein digestion, either by zymogen activation or facilitating substrate cleavage. This protease network operates optimally in acidic pH compartments either in the gut lumen or in vacuoles of the intestinal lining cells. Defining the role of each of these major enzymes now provides a clearer understanding of the function of a complex protease network that is conserved throughout invertebrate evolution. It also provides insights into which of these proteases are logical targets for development of chemotherapy for schistosomiasis, a major global health problem. © 2006 by The American Society for Biochemistry and Molecular Biology, Inc.
Authors & Co-Authors
Delcroix, Melaine
United States, San Francisco
University of California, San Francisco
France, Lille
Institut Pasteur de Lille
Sajid, Mohammed
United States, San Francisco
University of California, San Francisco
Caffrey, Conor Robert
United States, San Francisco
University of California, San Francisco
Lim, Kee Chong
United States, San Francisco
University of California, San Francisco
Dvořák, Jan
United States, San Francisco
University of California, San Francisco
Hsieh, Ivy
United States, San Francisco
University of California, San Francisco
Bahgat, Mahmoud Mohamed
Egypt, Giza
National Research Centre
Dissous, Colette
France, Lille
Institut Pasteur de Lille
McKerrow, James Hobson
United States, San Francisco
University of California, San Francisco
Statistics
Citations: 212
Authors: 9
Affiliations: 3
Identifiers
Doi:
10.1074/jbc.M607128200
ISSN:
00219258
e-ISSN:
1083351X
Research Areas
Cancer
Infectious Diseases