Structural insights into the catalytic mechanism of Trypanosoma cruzi trans-sialidase.
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.
Amaya
María Fernanda
MF
Unité de Biochimie Structurale, CNRS URA 2185, Institut Pasteur, 25 rue du Dr. Roux, 75724 Paris, France.
Watts
Andrew G
AG
Damager
Iben
I
Wehenkel
Annemarie
A
Nguyen
Tong
T
Buschiazzo
Alejandro
A
Paris
Gastón
G
Frasch
A Carlos
AC
Withers
Stephen G
SG
Alzari
Pedro M
PM
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
D006023:Glycoproteins; C069715:trans-sialidase; D009439:Neuraminidase