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• W2031313247 endingPage "14066" @default.
• W2031313247 startingPage "14061" @default.
• W2031313247 abstract "Within hours after the ingestion of a blood meal, the mosquito midgut epithelium synthesizes a chitinous sac, the peritrophic matrix. Plasmodium ookinetes traverse the peritrophic matrix while escaping the mosquito midgut. Chitinases (EC 3.2.1.14) are critical for parasite invasion of the midgut: the presence of the chitinase inhibitor, allosamidin, in an infectious blood meal prevents oocyst development. A chitinase gene, PgCHT1, recently has been identified in the avian malaria parasite P. gallinaceum. We used the sequence of PgCHT1 to identify a P. falciparum chitinase gene, PfCHT1, in the P. falciparum genome database. PfCHT1 differs from PgCHT1 in that the P. falciparum gene lacks proenzyme and chitin-binding domains. PfCHT1 was expressed as an active recombinant enzyme in Escherichia coli. PfCHT1 shares with PgCHT1 a substrate preference unique to Plasmodium chitinases: the enzymes cleave tri- and tetramers of GlcNAc from penta- and hexameric oligomers and are unable to cleave smaller native chitin oligosaccharides. The pH activity profile of PfCHT1 and its IC(50) (40 nM) to allosamidin are distinct from endochitinase activities secreted by P. gallinaceum ookinetes. Homology modeling predicts that PgCHT1 has a novel pocket in the catalytic active site that PfCHT1 lacks, which may explain the differential sensitivity of PfCHT1 and PgCHT1 to allosamidin. PfCHT1 may be the ortholog of a second, as yet unidentified, chitinase gene of P. gallinaceum. These results may allow us to develop novel strategies of blocking human malaria transmission based on interfering with P. falciparum chitinase." @default.
• W2031313247 created "2016-06-24" @default.
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• W2031313247 date "1999-11-23" @default.
• W2031313247 modified "2023-10-12" @default.
• W2031313247 title "The chitinase PfCHT1 from the human malaria parasite <i>Plasmodium falciparum</i> lacks proenzyme and chitin-binding domains and displays unique substrate preferences" @default.
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• W2031313247 doi "https://doi.org/10.1073/pnas.96.24.14061" @default.
• W2031313247 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/24190" @default.
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