Proteolysis of human hemoglobin by schistosome cathepsin D

Brindley, P. J., Kalinna, B. H., Wong, J. Y. M., Bogitsh, B. J., King, L. T., Smyth, D. J., Verity, C. K., Abbenante, G., Brinkworth, R. I., Fairlie, D. P., Smythe, M. L., Milburn, P. J., Bielefeldt-Ohmann, H., Zheng, Y. and McManus, D. P. (2001) Proteolysis of human hemoglobin by schistosome cathepsin D. Molecular And Biochemical Parasitology, 112 1: 103-112. doi:10.1016/S0166-6851(00)00351-0

Author Brindley, P. J.
Kalinna, B. H.
Wong, J. Y. M.
Bogitsh, B. J.
King, L. T.
Smyth, D. J.
Verity, C. K.
Abbenante, G.
Brinkworth, R. I.
Fairlie, D. P.
Smythe, M. L.
Milburn, P. J.
Bielefeldt-Ohmann, H.
Zheng, Y.
McManus, D. P.
Title Proteolysis of human hemoglobin by schistosome cathepsin D
Journal name Molecular And Biochemical Parasitology   Check publisher's open access policy
ISSN 0166-6851
Publication date 2001
Sub-type Article (original research)
DOI 10.1016/S0166-6851(00)00351-0
Volume 112
Issue 1
Start page 103
End page 112
Total pages 10
Place of publication Amsterdam
Publisher Elsevier Science Bv
Language eng
Subject 270000 Biological Sciences
Abstract Schistosomes feed on human blood. They employ proteases to degrade hemoglobin from ingested erythrocytes, using the residues released for amino acid metabolism. However, the identity and the role of the participating protease(s) are unclear and controversial. Confocal microscopy localized schistosomal cathepsin D to the parasite gastrodermis, and revealed elevated protease expression in females. At sub-cellular level, cathepsin D was localized to superficial digestive vacuoles of the gut and to cisternae of the gastrodermal rough endoplasmic reticulum. Schistosome cathepsin D, expressed in insect cells, autoactivated at pH 3.6 to a similar to 40 kDa form that cleaved the substrates o-aminobenzoyl-Ile-Glu-Phe-nitroPhe-Arg-NH2 and hemoglobin. The NH2-terminal residues of mature cathepsin D of Schistosoma japonicum and Schistosoma mansoni were Asn1 and Gly1, respectively, revealing that the proregion peptide was comprised of 35 residues. The proteases cleaved hemoglobin at pH 2.5-4.6, releasing numerous fragments. S. Japonicum cathepsin D cleaved at 13 sites, S. mansoni cathepsin D at 15 sites. Early cleavage sites were alpha Phe33-Leu34 and beta Phe41-Phe42, while others included alpha Leu109-Ala-110 and beta Leu14-Trp15, demonstrating a preference for bulky hydrophobic residues at pi and P1'. Most of the schistosomal cathepsin D cleavage sites were discrete from those of human cathepsin D. The gastrodermal location, elevated expression in females, acidic pH optima, similar substrate preferences in two species, and the discrete substrate preferences compared with human cathepsin D together provide compelling support for the hypothesis that schistosomal cathepsin D plays an integral role in hemoglobin proteolysis, and might be selectively targeted by drugs based on protease inhibition. (C) 2001 Elsevier Science B.V. All rights reserved.
Keyword Biochemistry & Molecular Biology
cathepsin D
aspartic protease
Host Hemoglobin
Adult Worms
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Unknown

Document type: Journal Article
Sub-type: Article (original research)
Collection: Institute for Molecular Bioscience - Publications
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Created: Wed, 19 Sep 2007, 17:00:39 EST