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Structural basis of sialyltransferase activity in trypanosomal sialidases
Author(s) -
Buschiazzo Alejandro,
Tavares Gisele A.,
Campetella Oscar,
Spinelli Silvia,
Cremona Marfa L.,
París Gastón,
Fernanda Amaya Maria,
Frasch Alberto C.C.,
Alzari Pedro M.
Publication year - 2000
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/19.1.16
Subject(s) - biology , sialyltransferase , trypanosoma cruzi , sialidase , biochemistry , trypanosoma , transferase , active site , binding site , sialic acid , enzyme , virology , neuraminidase , parasite hosting , world wide web , computer science
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 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 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.