title: Structural insights into the catalytic mechanism of Trypanosoma cruzi trans-sialidase.
abstract: Sialidases are a superfamily of sialic-acid-releasing enzymes that are of significant interest due to their implication as virulence factors in the pathogenesis of a number of diseases. However, extensive studies of viral and microbial sialidases have failed to provide a comprehensive picture of their mechanistic properties, in part because the structures of competent enzyme-substrate complexes and reaction intermediates have never been described. Here we report these structures for the Trypanosoma cruzi trans-sialidase (TcTS), showing that catalysis by sialidases occurs via a similar mechanism to that of other retaining glycosidases, but with some intriguing differences that may have evolved in response to the substrate structure.
authors.affiliation: Unité de Biochimie Structurale, CNRS URA 2185, Institut Pasteur, 25 rue du Dr. Roux, 75724 Paris, France.
authors.forename: María Fernanda
authors.initials: MF
authors.lastname: Amaya
authors.forename: Andrew G
authors.initials: AG
authors.lastname: Watts
authors.forename: Iben
authors.initials: I
authors.lastname: Damager
authors.forename: Annemarie
authors.initials: A
authors.lastname: Wehenkel
authors.forename: Tong
authors.initials: T
authors.lastname: Nguyen
authors.forename: Alejandro
authors.initials: A
authors.lastname: Buschiazzo
authors.forename: Gastón
authors.initials: G
authors.lastname: Paris
authors.forename: A Carlos
authors.initials: AC
authors.lastname: Frasch
authors.forename: Stephen G
authors.initials: SG
authors.lastname: Withers
authors.forename: Pedro M
authors.initials: PM
authors.lastname: Alzari
mesh_terms: D000818:Animals; D020134:Catalytic Domain; D018360:Crystallography, X-Ray; D006023:Glycoproteins / Q000737:chemistry* / Q000302:isolation & purification / Q000378:metabolism; D009439:Neuraminidase / Q000737:chemistry* / Q000302:isolation & purification / Q000378:metabolism; D017434:Protein Structure, Tertiary; D055672:Static Electricity; D014349:Trypanosoma cruzi / Q000737:chemistry* / Q000201:enzymology / Q000378:metabolism
chemical_list: D006023:Glycoproteins; C069715:trans-sialidase; D009439:Neuraminidase