| Proteolytic degradation of hemoglobin in the intestine of the human hookworm Necator americanus. | |
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MedLine Citation:
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PMID: 19434933 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Blood-feeding parasites use mechanistically distinct proteases to digest hemoglobin (Hb), often as multienzyme cooperative cascades. We investigated the roles played by 3 distinct proteases from adults of the human hookworm Necator americanus. The aspartic protease Na-APR-1 and the cysteine protease Na-CP-3 were expressed in catalytically active form in yeast, and the metalloprotease Na-MEP-1 was expressed in catalytically active form in baculovirus. Antibodies to all 3 proteases were used to immunolocalize each native enzyme to the intestine of adult N. americanus. Recombinant Na-APR-1 cleaved intact human Hb. In contrast, Na-CP-3 and Na-MEP-1 could not cleave Hb but instead cleaved globin fragments that had been hydrolyzed by Na-APR-1, implying an ordered process of hemoglobinolysis. Seventy-four cleavage sites within Hb alpha- and beta-chains were characterized after digestion with all 3 proteases. All of the proteases demonstrated promiscuous subsite specificities within Hb; noteworthy preferences included aromatic and hydrophobic P1 residues and hydrophobic P1' residues for Na-APR-1 and hydrophobic P1 residues for Na-MEP-1. We conclude that Hb digestion in N. americanus involves a network of distinct proteases, some of which act in an ordered fashion, providing a potential mechanism by which some of these hemoglobinases exert their efficacy as recombinant vaccines against hookworm infection. |
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Authors:
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Najju Ranjit; Bin Zhan; Brett Hamilton; Deborah Stenzel; Jonathan Lowther; Mark Pearson; Jeffrey Gorman; Peter Hotez; Alex Loukas |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: The Journal of infectious diseases Volume: 199 ISSN: 0022-1899 ISO Abbreviation: J. Infect. Dis. Publication Date: 2009 Mar |
Date Detail:
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Created Date: 2009-05-12 Completed Date: 2009-05-29 Revised Date: 2009-11-19 |
Medline Journal Info:
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Nlm Unique ID: 0413675 Medline TA: J Infect Dis Country: United States |
Other Details:
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Languages: eng Pagination: 904-12 Citation Subset: AIM; IM |
Affiliation:
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Helminth Biology Laboratory, Division of Infectious Diseases, Queensland Institute of Medical Research, Australia. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Amino Acid Sequence Animals Aspartic Acid Endopeptidases / metabolism Catalysis Cloning, Molecular Hemoglobins / chemistry, genetics, metabolism* Humans Hydrolysis Kinetics Molecular Sequence Data Necator americanus / enzymology, metabolism* Necatoriasis / immunology, metabolism* Peptide Fragments / chemistry, metabolism Peptide Hydrolases / metabolism Plasmodium falciparum / metabolism Recombinant Proteins / metabolism |
| Chemical | |
Reg. No./Substance:
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0/Hemoglobins; 0/Peptide Fragments; 0/Recombinant Proteins; 137597-31-0/alpha(A) globin; EC 3.4.-/Peptide Hydrolases; EC 3.4.23.-/Aspartic Acid Endopeptidases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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