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Title

Detailed insights from microarray and crystallographic studies into carbohydrate recognition by microneme protein 1 (MIC1) of Toxoplasma gondii

Authors
Garnett, James A.
Liu, Yan
Leon, Ester
Allman, Sarah A.
Saouros, Savvas
Curry, Stephen
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Published in Protein Science. 2009, vol. 18, no. 9, p. 1935-1947
Abstract The intracellular protozoan Toxoplasma gondii is among the most widespread parasites. The broad host cell range of the parasite can be explained by carbohydrate microarray screening analyses that have demonstrated the ability of the T. gondii adhesive protein, TgMIC1, to bind to a wide spectrum of sialyl oligosaccharide ligands. Here, we investigate by further microarray analyses in a dose-response format the differential binding of TgMIC1 to 2-3- and 2-6-linked sialyl carbohydrates. Interestingly, two novel synthetic fluorinated analogs of 3'SiaLacNAc(1-4) and 3'SiaLacNAc(1-3) were identified as highly potent ligands. To understand the structural basis of the carbohydrate binding specificity of TgMIC1, we have determined the crystal structures of TgMIC1 micronemal adhesive repeat (MAR)-region (TgMIC1-MARR) in complex with five sialyl-N-acetyllactosamine analogs. These crystal structures have revealed a specific, water-mediated hydrogen bond network that accounts for the preferential binding of TgMIC1-MARR to arrayed 2-3-linked sialyl oligosaccharides and the high potency of the fluorinated analogs. Furthermore, we provide strong evidence for the first observation of a C--F...H--O hydrogen bond within a lectin-carbohydrate complex. Finally, detailed comparison with other oligosaccharide-protein complexes in the Protein Data Bank (PDB) reveals a new family of sialic-acid binding sites from lectins in parasites, bacteria, and viruses.
Identifiers
PMID: 19593815
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Structures
Research group Biologie d'un parasite intracellulaire obligatoire (773)
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(ISO format)
GARNETT, James A. et al. Detailed insights from microarray and crystallographic studies into carbohydrate recognition by microneme protein 1 (MIC1) of Toxoplasma gondii. In: Protein Science, 2009, vol. 18, n° 9, p. 1935-1947. https://archive-ouverte.unige.ch/unige:3968

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Deposited on : 2009-11-05

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