Please use this identifier to cite or link to this item:
https://www.arca.fiocruz.br/handle/icict/32241
SUBSTRATE SPECIFICITY OF THE TRYPANOSOMA CRUZI TRANS-SIALIDASE
Author
Affilliation
New York University Medical Center. Department of Pathology. Division of Immunology. New York, NY, USA.
Escola Paulista de Medicina. Disciplina de Biologia Celular. São Paulo, SP, Brasil.
Escola Paulista de Medicina. Disciplina de Biologia Celular. São Paulo, SP, Brasil.
Escola Paulista de Medicina. Disciplina de Biologia Celular. São Paulo, SP, Brasil.
Gifu University. Department of Applied Bioorganic Chemistry. Gifu, Japan.
Gifu University. Department of Applied Bioorganic Chemistry. Gifu, Japan.
Gifu University. Department of Applied Bioorganic Chemistry. Gifu, Japan.
Escola Paulista de Medicina. Disciplina de Biologia Celular. São Paulo, SP, Brasil.
Escola Paulista de Medicina. Disciplina de Biologia Celular. São Paulo, SP, Brasil.
Escola Paulista de Medicina. Disciplina de Biologia Celular. São Paulo, SP, Brasil.
Escola Paulista de Medicina. Disciplina de Biologia Celular. São Paulo, SP, Brasil.
Gifu University. Department of Applied Bioorganic Chemistry. Gifu, Japan.
Gifu University. Department of Applied Bioorganic Chemistry. Gifu, Japan.
Gifu University. Department of Applied Bioorganic Chemistry. Gifu, Japan.
Escola Paulista de Medicina. Disciplina de Biologia Celular. São Paulo, SP, Brasil.
Abstract
Trypanosoma cruzi trypomastigotes acquire sialic acid (SA)
from host glycoconjugates by means of a plasma membraneassociated
trans-sialidase (TS). Here we study the substrate
specificity of TS, which differs from all known sialyltransferases
in that it does not require cytidine monophosphate
(CMD-SA as donor. The T.cruzi TS reversibly
transfers SA to saccharides with terminal /3-Gal (but not
a-Gal) residues. Donors are saccharides with SA linked to
terminal /3-Gal residues by (a2-3), but not (a2-6) bonds. The
type of /3-linkage of the terminal Gal residue is of minor
importance (/31-4 and 01-6 are slightly better than /Sl-3),
whereas chain length and the structure of additional vicinal
sugar residues are not relevant. SA on the surface of living
trypomastigotes of T. cruzi is transferred back and forth
between the parasite surface and acceptor molecules with
terminal /3-Gal, either in solution or on the surface of
neighbouring mammalian cells. Addition of fucose residue
on or close to the terminal galactose impairs TS activity. As
a consequence, the enzyme acts poorly on the E-selectin
ligand sialyl-Lewis" and its precursor Lewis1, and in vitro
adhesion of TS-treated neutrophils to L-cells expressing
L-selectin is not affected. Modifications in the structure of
the (a2-3)-linked iV-acetyl-neuraminic acid (Neu5Ac) (deoxy
or methoxv) of the donor molecules do not impair transfer
if the changes are at C9, whereas changes at C4, C7 and C8
impair the ability to donate the modified SA. Compounds
with modified C4 and C8 inhibit TS at relatively high
inhibitor/substrate ratios.
Share