Trypanosoma cruzi Trans-Sialidase: Structural Features and Biological Implications
Trypanosoma cruzi trans-sialidase (TcTS) has intrigued researchers all over the world since it was shown that T. cruzi incorporates sialic acid through a mechanism independent of sialyltransferases. The enzyme has being involved in a vast myriad of functi
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Trypanosoma cruzi Trans-Sialidase: Structural Features and Biological Implications Isadora A. Oliveira, Leonardo Freire-de-Lima, Luciana L. Penha, Wagner B. Dias, and Adriane R. Todeschini
Abstract Trypanosoma cruzi trans-sialidase (TcTS) has intrigued researchers all over the world since it was shown that T. cruzi incorporates sialic acid through a mechanism independent of sialyltransferases. The enzyme has being involved in a vast myriad of functions in the biology of the parasite and in the pathology of Chagas’ disease. At the structural level experiments trapping the intermediate with fluorosugars followed by peptide mapping, X-ray crystallography, molecular modeling and magnetic nuclear resonance have opened up a three-dimensional understanding of the way this enzyme works. Herein we review the multiple biological roles of TcTS and the structural studies that are slowly revealing the secrets underlining an efficient sugar transfer activity rather than simple hydrolysis by TcTS.
Abbreviations 4-MUNeu5Ac Galf Galp GlcNAc Neu5Ac Neu5Gc NGF pNPNeu5Ac SAPA
4-methylumbelliferyl-N-acetyl neuraminic acid Galactofuranose Galactopyranose N-acetylglucosamine N-acetylneuraminic N-glycolylneuraminic acid Nerve growth factor receptor p-nitrophenyl-N-acetyl-neuraminic acid Shed acute phase antigen
I.A. Oliveira • L. Freire-de-Lima • L.L. Penha • W.B. Dias • A.R. Todeschini (*) Laboratório de Glicobiologia Estrutural e Funcional, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Avenida Carlos Chagas Filho, 373, Centro de Ciências da Saúde-Bloco D-3, Cidade Universitária, 21941-902 Rio de Janeiro, Brazil e-mail: [email protected] A.L.S. Santos et al. (eds.), Proteins and Proteomics of Leishmania and Trypanosoma, Subcellular Biochemistry 74, DOI 10.1007/978-94-007-7305-9_8, © Springer Science+Business Media Dordrecht 2014
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Sias Siglecs TcTS TSs UTR
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Sialic acids Sia-binding Ig-like lectin Trypanosoma cruzi trans-sialidase Trans-sialidase family Untranslated regions
Introduction
The initiation of communication between Trypanosoma cruzi, the etiologic agent of Chagas’ disease, and mammalian cells requires contact between parasite molecules and host ligands. The parasite membrane is covered with a dense coat formed mainly of molecules of the trans-sialidase (TSs) family and of sialic acids (Sias) containing glycoproteins; this coat assures an interface with the host environment (Freitas et al. 2011; De Pablos and Osuna 2012). Sias are acidic monosaccharides found at the outermost ends of the sugar chains of glycoconjugates involved in a myriad of functions ranging from cell recognition to cell life and death (Varki 2006). T. cruzi is not able to synthesize Sias by the well-known route in which cytidine monophosphate-sialic acid is an intermediate. Instead, T. cruzi is part of a restrict group of parasites evolutionarily adapted to incorporate sialic acid from exogenous sialoglycoconjugates by means of a glycoside hydrolase known as transsialidase (TcT
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