Trypanosoma cruzi trans-sialidases mechanism

M. F. Amaya, A. G. Watts, I. Damager, A. Wehenkel, T. Nguyen, A. Buschiazzo, G. Paris, A. C. C. Frasch, S. G. Withers, and P. M. Alzari, Structural insights into the catalytic mechanism of Trypanosoma cruzi trans-sialidase, Structure, 12 (2004) 775-784. 

M. Ribeirao, V. L. Pereira-Chioccola, D. Eichinger, M. M. Rodrigues, and S. Schenkman, Temperature differences for frans-glycosylation and hydrolysis reaction reveal an acceptor binding site in the catalytic mechanism of Trypanosoma cruzi trans-sialidase, Glycobiology, 1 (1997) 1237-1246. 

M. J. M. Alves and W. Colli, Role of the gp85/trans-sialidase superfamily of glycoproteins in the interaction of Trypanosoma cruzi with host structures, in B. A. Burleigh and D. Soldati-Favre, (Eds.), Molecular Mechanisms of Parasite Invasion, 47 pp. 58-96. 

A. R. Todeschini, W. B. Dias, M. F. Girard, J. M. Wieruszeski, L. Mendonga-Previato, and J. O. Previato, Enzymatically inactive trans-sialidase from Trypanosoma cruzi binds sialyl and beta-galactopyranosyl residues in a sequential ordered mechanism, J. Biol. Chem., 279 (2004) 5323-5328. 

Abstract In contrast to the general hydrolases, trans-sialidase from Trypanosoma cruzi (TcTS) shows excellent regio- and stereoselectivity as well as high yields in transfer reactions. Discussed are the occurrence of trans-sialidases and studies on the transfer mechanism. In detail, the preparative use by chemoenzymatic syntheses with TcTS are outlined with emphasis on the design of modified donor and acceptor substrates. Another section focuses on attempts to develop inhibitors for TcTS, and these endeavors are based on donor- and acceptor-inspired modifications as well as on some completely different structures. 

Based on the invasion mechanism for mammals by Trypanosoma cruzi, a promising approach to tackle Chagas disease would be to modulate or better inhibit trans-sialidase as recently discussed by Neres et al. [51]. 

---