Trans-sialidases, trypanosomal

NeuSAc is a weak inhibitor of classical sialidases but does not act at all on the trans-sialidases. Correspondingly, the 2,3-difluoro derivative of NeuSAc, forming a covalent intermediate with sialidases and trans-sialidases (see later) was required at high concentrations (20 mM) to inactivate the enzyme completely Since trans-sialidases possess a lactose-binding site in their active center (as described next), lactose and its derivatives, especially lactitol, inhibit the sialic acid transfer of the enzyme from T. cruzi. Oligosaccharides from the mucins of this trypanosome can also inhibit the transfer of sialic acid to, for example, the substrate A-acetyllactosa-mine. It should be noted that heavy metal ions, especially merciuy, are potent inhibitors of sialidases and trans-sialidases. The latter enzymes do not require calcium ions, in contrast to some siaUdases. " " " ... 

Two trans-sialidases isolated from the animal-pathogenic Afiican trypanosome T. Congo lense show pronounced differences in their capacity for sialic acid transfer as compared with the hydrolytic activity. Partial sequences were obtained from these two enzymes by a PCR-based approach, showing 50% identity with each oflier, but are similar to viral, bacterial, animal siahdases and other trans-sialidases. Most of the critical active-site residues common to other trypanosomal siahdases and TS are conserved This similarity, together with the amino acid difference at the active site, between American and African (trans-)siahdases is depicted in the pubUcation. ... 

E. Medina-Acosta, S. Paul, S. Tomlinson, and L. C. Pontes-de-Carvalho, Combined occurrence of trypanosomal sialidase/trans-sialidase activities and leishmanial metalloproteinase gene homologues in Endotrypanum sp, Mol. Biochem. Parasitol, 64 (1994) 273-282. 

A.R. Todeschini, M. P. Nunes, R. S. Pires, M. F. Lopes, J. O. Previato, L. Mendonea-Previato, and G. A. DosReis, Costimulation of host T lymphocytes by a trypanosomal trans-sialidase Involvement of CD43 signaling, J. Immunol, 168 (2002) 5192-5198. 

Trypanosomal Trans-sialidases Valuable Synthetic Tools and Targets for Medicinal Chemistry... 

Aisaka /fl/., 1991 Heuermann a/., 1991 Hoyer era/., 1991 Tanakaer al., 1992 Engstler et al., 1992, 1994 Zenz et al., 1993). The only common property is the acidic pH optimum (pH 5.0-6.1), though the trypanosomal trans-sialidases exhibit maximum activity at a neutral pH (Engstler et al., 1993). As these properties did not reveal any relationship between microbial sialidases, the enzymes were further investigated on the DNA level, from which interesting information became available. 

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