Skip to Main content Skip to Navigation
Journal articles

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.
Complete list of metadata

Cited literature [28 references]  Display  Hide  Download
Contributor : Alejandro Buschiazzo Connect in order to contact the contributor
Submitted on : Friday, April 24, 2020 - 11:20:47 PM
Last modification on : Thursday, January 13, 2022 - 2:20:44 PM

Links full text




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⟩



Les métriques sont temporairement indisponibles