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EMBO J. 2000 Jan 4;19(1):16-24.

Structural basis of sialyltransferase activity in trypanosomal sialidases.

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1
Unité de Biochimie Structurale, Institut Pasteur, 25 rue du Dr Roux, 75724 Paris.

Abstract

The intracellular parasite Trypanosoma cruzi, the etiological agent of Chagas disease, sheds a developmentally regulated surface trans-sialidase, which is involved in key aspects of parasite-host cell interactions. Although it shares a common active site architecture with bacterial neuraminidases, the T.cruzi enzyme behaves as a highly efficient sialyltransferase. Here we report the crystal structure of the closely related Trypanosoma rangeli sialidase and its complex with inhibitor. The enzyme folds into two distinct domains: a catalytic beta-propeller fold tightly associated with a lectin-like domain. Comparison with the modeled structure of T.cruzi trans-sialidase and mutagenesis experiments allowed the identification of amino acid substitutions within the active site cleft that modulate sialyltransferase activity and suggest the presence of a distinct binding site for the acceptor carbohydrate. The structures of the Trypanosoma enzymes illustrate how a glycosidase scaffold can achieve efficient glycosyltransferase activity and provide a framework for structure-based drug design.

PMID:
10619840
PMCID:
PMC1171773
DOI:
10.1093/emboj/19.1.16
[Indexed for MEDLINE]
Free PMC Article
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