Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.1.53 (sialidase)
 2,694 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Trypanosoma cruzi attaches and invades a large variety of mammalian cells by receptor-mediated interactions, one of them involving the binding of parasite trans-sialidase to host sialyl receptors. Three proteoglycan-deficient mutants of Chinese hamster ovary (CHO) cells were used to probe the role of host heparin and heparan sulfate glycosaminoglycans (GAG) in T. cruzi invasion. All three mutants supported adhesion and infection to a much lower extent than the parental CHO cells. One of the mutants, pgsD-677, did not express heparan sulfate while containing three- to four-fold excess chondroitin sulfate, yet the cell line was a poor substrate for T. cruzi adhesion. Proteoglycan-deficient cells obtained by inhibiting GAG synthesis in parental cells with p-nitrophenyl-beta-D-xyloside, were also poor hosts for T. cruzi invasion. Furthermore, digestion of parental cells with heparinase and heparitinase, two lyases that specifically depolymerize heparin and heparan sulfate, reduced the potential of the cells to support T. cruzi adhesion and growth. Lyases that digested chondroitin sulfate and other GAGs did not affect T. cruzi invasion. These results suggest that heparin/heparan sulfate epitopes are receptors for T. cruzi invasion. The corresponding counter-receptor on T. cruzi appears to be penetrin, a heparin-binding protein that promotes trypanosome penetration into cells. Purified penetrin caused agglutination of red blood cells, and the hemagglutination was exquisitely sensitive to heparin and heparan sulfate. However, sialic acid and sialyl compounds did not inhibit penetrin-induced hemagglutination. Recombinant penetrin competitively inhibited T. cruzi invasion of proteoglycan-containing parental cells, but not of proteoglycan-deficient mutants nor of heparitinase-treated cells. Furthermore, consistent with the sugar specificity of penetrin as a hemagglutinin, recombinant penetrin competed for trypanosome invasion of a CHO cell mutant (Lec2) that expresses heparan sulfate but not sialyl residues. Given that the release of sialic acid from the proteoglycan-deficient mutants further reduced T. cruzi invasion, as did the removal of heparan sulfate from the Lec2 mutant, and given that penetrin does not bind to sialic acid with high affinity, the results indicate that the penetrin-heparan sulfate pathway for T. cruzi invasion is distinct from the trans-sialidase-sialic acid route.
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PMID:Mediation of Trypanosoma cruzi invasion by heparan sulfate receptors on host cells and penetrin counter-receptors on the trypanosomes. 793 30

Platelet factor 4 is a heparin-binding protein released from the alpha granules of activated platelets. This study describes the purification and identification of two forms of rat platelet factor 4, the previously characterized non-glycosylated form of 7 kDa and an additional glycosylated form of molecular mass 9 kDa. The two proteins both neutralized the antithrombin-III-dependent inhibitory activity of heparin. Although their amino acid composition was found to be the same, in the N-terminal sequence of the 9-kDa protein, the second threonine residue could not be detected and a difference of 976Da was determined by mass spectrometry. After digestion with O-glycanase and sialidase, the two proteins showed the same molecular mass. Overall consideration of these data led to identification of the higher-molecular-mass protein as a glycosylated form of rat platelet factor 4 with O-glycosylation at the second N-terminal amino acid, while the structure of the oligosaccharide core was established by mass spectrometry and sugar differentiation with lectins. The two forms of platelet factor 4 are both present in platelets and secreted after platelet activation.
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PMID:Rat platelets contain glycosylated and non-glycosylated forms of platelet factor 4. Identification and characterization by mass spectrometry. 803 93