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Structural basis of sialyltransferase activity in trypanosomal sialidases

Abstract : The intracellular parasite Trypanosoma cruzi, the etiol-ogical 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 β-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 sialyltransfer-ase 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 glycosyl-transferase activity and provide a framework for structure based drug design.
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Contributor : Alejandro Buschiazzo <>
Submitted on : Friday, April 24, 2020 - 11:20:47 PM
Last modification on : Thursday, May 14, 2020 - 1:29:03 AM

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Alejandro Buschiazzo, Gisele Tavares, Oscar Campetella, Silvia Spinelli, Maria Cremona, et al.. Structural basis of sialyltransferase activity in trypanosomal sialidases. EMBO Journal, EMBO Press, 2000, 19 (1), pp.16 - 24. ⟨10.1093/emboj/19.1.16⟩. ⟨pasteur-02554089⟩

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