Abstract

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"A broad spectrum Kunitz-type serine protease inhibitor secreted by the hookworm, Ancylostoma ceylanicum" Milstone, A.M.; Harrison, L.M.; Bungiro, R.D.; Kuzmic, P.; and Cappello, M. (2000) J. Biol. Chem. 275, 29391-9. Abstract: Although bloodfeeding hookworms infect over a billion people worldwide, little is known about the molecular mechanisms through which these parasitic nematodes cause gastrointestinal hemorrhage and iron deficiency anemia. A cDNA corresponding to a secreted Kunitz-type serine protease inhibitor has been cloned from adult Ancylostoma ceylanicum hookworm RNA. The translated sequence of the Ancylostoma ceylanicum Kunitz-type Inhibitor 1 (AceKI-1) cDNA predicts a 16 amino acid secretory signal sequence, followed by a 68 amino acid mature protein with a MW of 7889 Da and a methionine residue at its putative P1 inhibitory reactive site. Recombinant protein (rAceKI-1) was purified from induced lysates of E. coli transformed with the rAceKI-1/pET 28a plasmid, and in vitro studies demonstrate that rAceKI-1 inhibits the serine proteases chymotrypsin, pancreatic elastase, neutrophil elastase, and to a lesser extent, trypsin. AceKI-1 inhibitory activity is present in soluble protein extracts and excretory/secretory products of adult hookworms, but not the infective third stage larvae. The native AceKI-1 inhibitor has been purified to homogeneity from soluble extracts of adult A. ceylanicum using size exclusion and rpHPLC chromatographies. As a potent inhibitor of mammalian intestinal proteases, AceKI-1 may play a role in parasite survival and the pathogenesis of hookworm anemia.

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