Hookworm aspartic protease, Na-APR-2, cleaves human hemoglobin and serum proteins in a host-specific fashion

Williamson, A. L., Brindley, P. J., Abbenante, G., Datu, B. J. D., Prociv, P., Berry, C., Girdwood, K., Pritchard, D. I., Fairlie, D. P., Hotez, P. J., Zhan, B. and Loukas, A. (2003) Hookworm aspartic protease, Na-APR-2, cleaves human hemoglobin and serum proteins in a host-specific fashion. Journal of Infectious Diseases, 187 3: 484-494. doi:10.1086/367708


Author Williamson, A. L.
Brindley, P. J.
Abbenante, G.
Datu, B. J. D.
Prociv, P.
Berry, C.
Girdwood, K.
Pritchard, D. I.
Fairlie, D. P.
Hotez, P. J.
Zhan, B.
Loukas, A.
Title Hookworm aspartic protease, Na-APR-2, cleaves human hemoglobin and serum proteins in a host-specific fashion
Journal name Journal of Infectious Diseases   Check publisher's open access policy
ISSN 0022-1899
Publication date 2003
Sub-type Article (original research)
DOI 10.1086/367708
Volume 187
Issue 3
Start page 484
End page 494
Total pages 11
Editor Martin S. Hirsch
Place of publication Chicago
Publisher Univ Chicago Press
Collection year 2003
Language eng
Subject C1
320305 Medical Biochemistry - Proteins and Peptides
730101 Infectious diseases
Abstract Hookworms are voracious blood-feeders. The cloning and functional expression of an aspartic protease, Na-APR-2, from the human hookworm Necator americanus are described here. Na-APR-2 is more similar to a family of nematode-specific, aspartic proteases than it is to cathepsin D or pepsin, and the term nemepsins for members of this family of nematode-specific hydrolases is proposed. Na-apr-2 mRNA was detected in blood-feeding, developmental stages only of N. americanus, and the protease was expressed in the intestinal lumen, amphids, and excretory glands. Recombinant Na-APR-2 cleaved human hemoglobin (Hb) and serum proteins almost twice as efficiently as the orthologous substrates from the nonpermissive dog host. Moreover, only 25% of the Na-APR-2 cleavage sites within human Hb were shared with those generated by the related N. americanus cathepsin D, Na-APR-1. Antiserum against Na-APR-2 inhibited migration of 50% of third-stage N. americanus larvae through skin, which suggests that aspartic proteases might be effective vaccines against human hookworm disease.
Keyword Infectious Diseases
Adult Haemonchus-contortus
Ancylostoma-caninum
Cathepsin-d
Plasmodium-falciparum
Degradation
Binding
Pathway
Q-Index Code C1

 
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Created: Wed, 15 Aug 2007, 02:46:27 EST