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

Streptococcus suis capsular type 2 has a capsule rich in sialic acid (NANA). Sialic acid, known to be an antiphagocytic factor for many bacterial species, inhibits the activation of the alternative complement pathway. The role of capsular NANA in virulence, resistance to phagocytosis and intracellular survival of S. suis capsular type 2 was evaluated. In general, a low concentration of NANA was observed for all the S. suis strains tested. In addition, no difference could be found in NANA concentrations between strains of different virulence degrees. Sialic acid concentration increased in the virulent strain 89-1591 and the avirulent strain 90-1330 after in vivo growth with an increased capsular material thickness compared to growth in vitro. No significant difference could be found in the phagocytosis rate by porcine blood monocytes of either strain and strain 89-1591 treated with sialidase or the sialic acid-binding lectin from Sambucus nigra (SNA I). Intracellular survival of strain 89-1591 decreased after treatments with sialidase or lectin, becoming comparable to that of strain 90-1330. Finally, no difference could be seen in virulence using a murine model, even if strain 89-1591 was treated with the enzyme or the lectin. Thus, NANA does not seem to be a critical virulence factor for S. suis capsular type 2.
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PMID:Role of capsular sialic acid in virulence and resistance to phagocytosis of Streptococcus suis capsular type 2. 885 18

Previously, beta 1,3-galactosyltransferase-deficient (Tn+) and normal (TF+) T-lymphocyte clones have been established from a patient suffering from Tn-syndrome [Thurnher et al. (1992) Eur J Immunol 22: 1835-42]. Tn+ T lymphocytes express only Tn antigen GalNAc alpha 1-O-R) while other O-glycan structures such as sialosyl-Tn (Neu5Ac alpha 2,6GalNAc alpha 1-O-R) or TF (Gal beta 1-3GalNAc alpha 1-O-R) antigens are absent from these cells as shown by flow cytometry using specific mABs for TF and sialosyl-Tn antigen, respectively. Normal T lymphocytes express the TF antigen and derivatives thereof. The surface glycans of Tn+ and TF+ cells were then analysed by flow cytometry using the following sialic acid-binding lectins: Amaranthus caudatus (ACA), Maackia amurensis (MAA), Limax flavus (LFA), Sambucus nigra (SNA) and Triticum vulgare (WGA). Equal and weak binding of MAA and SNA to both TF+ and Tn+ cells was found. WGA, LFA and ACA bound more strongly to TF+ cells than to Tn+ cells. Binding of ACA to TF+ cells was enhanced after sialidase treatment. To investigate the possible biological consequences of hyposialylation, binding of three sialic acid-dependent adhesion molecules to Tn+ and TF+ cells was estimated using radiolabelled Fc-chimeras of sialoadhesin (Sn), myelin-associated glycoprotein (MAG) and CD22. Equal and strong binding of human CD22 to both TF+ and Tn+ cells was found. Whereas binding of Sn and MAG to TF+ cells was strong (100%), binding to Tn+ cells amounted only to 33% (Sn) and 19% (MAG). These results indicate that the in vivo interactions of T lymphocytes in the Tn syndrome with CD22 are not likely to be affected, whereas adhesion mediated by Sn or MAG could be strongly reduced.
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PMID:Constitutively hyposialylated human T-lymphocyte clones in the Tn-syndrome: binding characteristics of plant and animal lectins. 887 13

Sialidase activity in cell-free supernatant of batch-cultivated Chinese hamster ovary (CHO) cells producing human recombinant antithrombin III (rhAT III) was monitored during cultivation using 4-methylumbelliferyl substrate and HPLC for free sialic acid determination. Supernatant sialidase as well as lactate dehydrogenase activity increased significantly during batch growth. The enhanced number of dead cells correlated with increasing sialidase activity which seemed to be principally due to cell lysis, resulting in release of cytosolic sialidase. Loss of terminally alpha (2-->3) bound sialic acids of the oligosaccharides of rhAT III was analyzed in lectin-based Western blot and enzyme-linked lectin assays, using Maackia amurensis and Datura stramonium agglutinins for specific determination of Neu5Ac alpha (2-->3)Gal- and Gal beta (1-->4)-GlcNAc-terminated glycoproteins, respectively. Results show a remarkable loss of terminal sialic acids of rhAT III along with decrease in CHO cell viability and concomitant increase of dead cells throughout long-term batch cultivation. To avoid this degradation effect, process parameters forcing high viability are essential and harvesting of culture at an early time even at suboptimal recombinant protein concentration is highly recommended to avoid product desialylation.
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PMID:Sialidase activity in culture fluid of Chinese hamster ovary cells during batch culture and its effects on recombinant human antithrombin III integrity. 898 82

Simplified HPLC protocols to determine the activity and linkage specificity and to detect the most commonly-encountered contaminants in available exoglycosidase preparations (Jacob and Scudder, Methods Enzymol., 230, 280-300, 1994) were developed. Monosaccharides and oligosaccharides were analyzed in a single chromatographic step using high-pH anion-exchange chromatography with pulsed amperometric detection. All analyses were performed with underivatized oligosaccharide substrates and by direct injection of unprocessed, diluted enzyme digests into the chromatograph. The sialidase from Newcastle disease virus was found to release both alpha (2-->3)- and alpha (2-->6)-linked Neu5Ac from a triantennary, lactosamine-type oligosaccharide. The activity of alpha-galactosidase from green coffee beans was assayed using Gal alpha(1-->3)[Fuc-alpha(1ar2)]Gal by detection of Gal and Fuc alpha(1-->3)Gal. The linkage specificities of beta-galactosidases from Streptococcus pneumoniae and bovine testis were assessed using Gal beta(1-->3 or 4)GlcNAc beta(1-->3)beta(1-->4)Glc as substrates. Contaminating beta-N-acetylhexosaminidase activity in the beta-galactosidase preparation was assayed using an agalactobiantennary oligosaccharide. The alpha(1-->3 or 4) linkage specificity of fucosidase III from almond meal was confirmed (Scudder et al., J. Biol. Chem. 265, 16472-16477, 1990) by its inactivity against a biantennary oligosaccharide with all Fuc residues linked alpha(1-->6). An alpha-fucosidase from chicken liver was found to cleave alpha(1-->2,3 or 6)-linked Fuc residues from oligosaccharides. The activity of jack bean (Canavalia ensiformis) alpha-mannosidase was assayed with a relatively resistant substrate, Man alpha(1-->3)- Man beta(1-->4)GlcNAc. A GlcNAc beta(1-->4)-terminated triantennary oligosaccharide was used to assay for contaminating beta-N-acetylhexosaminidase activity in alpha-mannosidase preparations and to determine the linkage and branch specificity of beta-N-acetylhexosaminidase at different enzyme concentrations.
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PMID:Exoglycosidase purity and linkage specificity: assessment using oligosaccharide substrates and high-pH anion-exchange chromatography with pulsed amperometric detection. 887 65

Sulfated glycosaminoglycans are known to inhibit mammalian acid-active sialidase. Although the inhibition depends clearly on the presence of sulfate groups on these macromolecules, there was no information on the intrinsic inhibitory potency of inorganic sulfate. In this study, we demonstrate that inorganic sulfates inhibit acid-active Mu-Neu5Ac sialidase of U937 cells. This inhibition was found to be reversible and it appeared to be of the mixed competitive type. Sulfate-induced inhibition was also observed in other cells as well as with other substrates such as sialyl lactose and bovine mixed brain gangliosides. We conclude that the intrinsic inhibitory potency of sulfate groups may be significantly involved in the inhibition of acid-active sialidase by sulfated glycosaminoglycans. In addition, inorganic sulfate by its apparent potency to selectively inhibit acid sialidases might constitute an interesting tool for the characterisation of the minor forms of sialidases occurring in mammalian cells.
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PMID:Inhibition of acid sialidase by inorganic sulfate. 910 7

Compound 10b, 6-acetamido-6,8-dideoxy-D-erythro-beta-D- galacto-octopyranosyl-1-oxyacetic acid sodium salt, was synthesised by hydrazinolysis of Lincomycin, acetylation of methylthiolincosaminide (MTL) 9a, and by subsequent glycosylation of acetate 9b with methyl glycolate under mild conditions (NIS/TfOH). The methyl ester 10a was hydrolysed by treatment with Amberlite Ira-4OO (OH-) resin and aqueous sodium hydroxide, followed by neutralisation with Dowex-50 W x 8 (H+) resin and lyophilisation to give 10b. This carboxylate may represent the first derivative in a novel series of sialidase inhibitors utilising carbohydrate natural products. The phosphonate 11c, prepared under the same experimental conditions with dibenzyl(hydroxymethyl)phosphonate as acceptor, also displays an inhibitory activity towards Clostridium perfringens sialidase (Ki in mM range as with Neu5Ac).
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PMID:Carbohydrate natural products as a scaffolding for the preparation of potential neuraminidase inhibitors. 911 9

In search of substrate analogues for the porcine liver beta-D-Gal p-(1-->3)-D-Gal p-NAc: CMP-Neu5Ac-(2-->3')-alpha-sialyltransferase, three disaccharides beta-D-Gal p-(1-->3)-beta-D-Gal p-O-CH3 (5), beta-D-Gal p-(1-->3)-beta-D-(2-OAc)-Gal p-O-CH3 (7) and beta-D-Gal p-(1-->3)-beta-D-(2-OAc)-Gal p-O-Bn (11) were synthesized and tested with the enzyme. Disaccharide 7 turned out to be a very good substrate allowing a rapid access to the trisaccharide alpha-Neu5Ac-(2-->3)-beta-D-Gal p-(1-->3)-beta-D-(2-OAc)-Gal p-O-CH3 (13) on a preparative scale using the crude enzyme immobilized on cationic exchanger. Trisaccharide 13 was further exploited, first as a sialyl donor in Trypanosoma cruzi trans-sialidase catalyzed reaction and second through acetolysis reaction as a source for the synthon alpha-Neu5Ac-(2-->3)-D-Gal (16).
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PMID:Porcine liver (2-->3)-alpha-sialyltransferase: substrate specificity studies and application of the immobilized enzyme to the synthesis of various sialylated oligosaccharide sequences. 920 41

When compared to bacterial or viral sialidases, eukaryotic sialidases are expressed at lower levels and frequently show poor specific activities. The identification and characterization of sialidases from eukaryotes have been slowed down due to the limited sensitivity of available sialidase substrates. Therefore, we chemically synthesized a fluorogenic compound, 4-trifluoromethylumbelliferyl-alpha-D-N-acetylneuraminic acid (CF3MU-Neu5Ac), and tested its use as a substrate for eight different sialidases, including enzymes from viral, bacterial, and eukaryotic sources. Kinetic analysis revealed CF3MU-Neu5Ac to be a very sensitive sialidase substrate. Furthermore, this substance proves to be perfectly suitable for the in vivo examination of sialidases and for the detection of recombinant sialidase by means of expression cloning.
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PMID:Chemical synthesis of 4-trifluoromethylumbelliferyl-alpha-D-N-acetylneuraminic acid glycoside and its use for the fluorometric detection of poorly expressed natural and recombinant sialidases. 924 36

Clusterin is a N-glycosylated sialoglycoprotein present in rat brain cells. Clusterin, which elicits aggregation in a wide variety of cells, has been suggested to play an important role in synaptic remodeling through its cell adhesion property or lipid transport capacity in the brain. Sialic acid residues in clusterin may be responsible for its structural conformation, stability and functional ability. Maturation of clusterin is governed by the relative actions of sialyltransferases and sialidases that are present in brain microsomes, golgi bodies, cytosol and plasma membranes. We have earlier reported that chronic ethanol treatment in rats has a damaging effect on the hepatic glycosylation machinery. Others have reported increased hydrolysis of brain sialoconjugates in rats following chronic ethanol administration. Specificity of the effects of chronic ethanol treatment in the brain in relation to the glycosylation process, is still obscure. Therefore, in this investigation, we have studied the specific effects of chronic ethanol treatment on the glycosylation of rat brain clusterin and the causes that may lead to any possible defects in the glycosylation process. We have determined the effects of chronic ethanol treatment on (i) the incorporation of labeled leucine and N-acetylmannosamine into immunoprecipitable clusterin in whole brain homogenate, microsomes, golgi, cytosol, plasma membrane and synaptosomes, (ii) enzymatic activities of sialyltransferases in golgi and synaptosomes, and sialidase in brain cytosol and plasma membranes, and (iii) de novo synthetic rate of rat brain cytosolic sialidase. Our results showed that chronic ethanol treatment in rats resulted in (1) a decreased sialation index of brain clusterin by 47. 2% (p<0.001), 56.7% (p<0.05), 51.7% (p<0.05), 64.8% (p<0.001), and 54.5% (p<0.05), respectively, in whole brain homogenate, golgi, cytosol, plasma membranes, and synaptosomes; (2) a 46.1% (p<0.05) and 12.5% (p<0.05) decreased activities of brain sialyltransferases, respectively, in the golgi and the synaptosomal fractions; (3) a 70. 1% (p<0.05) and 42.6% (p<0.05) increased activities of sialidases, respectively, in the cytosol and plasma membrane fractions; and (4) a 22.2%-64.3% (p<0.001) increased incorporation of labeled leucine into brain cytosolic sialidase. Our findings have clearly established that long-term ethanol treatment in rats leads to a marked impairment in the glycosylation of rat brain clusterin as a result of altered activities of brain sialation and desialation enzymes. In particular, the specific increase noted in brain sialidase activity was due to concomitant increases in its synthetic rate. These defects in the glycosylation of brain clusterin may lead to changes in the molecular conformation of clusterin, and thus, may result in its structural instability and/or functional impairment.
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PMID:Deleterious actions of chronic ethanol treatment on the glycosylation of rat brain clusterin. 952 71

Sialyl-linkage specificity of sialidases of the human influenza A virus strains, A/Aichi/2/68 (H3N2) and A/PR/8/34 (H1N1) were studied using natural and synthetic gangliosides. The sialidase of the A/Aichi/2/68 strain hydrolyzed the terminal Neu5Acalpha2-3Gal sequence but not the Neu5Acalpha2-3 linkage on the inner Gal of GM1a, which is a ganglioside that has the gangliotetraose chain (Galbeta1-3GalNAcbeta1-4-(Neu5Acalpha2-3)Galbeta1++ +-4Glcbeta1-Cer). The sialidase hydrolyzed the Neu5Ac on the inner Gal of GM2, which had a shorter gangliotriose chain. GM4, which had the shortest chain (Neu5Acalpha2-3Galbeta1-Cer) of the gangliosides, had a lower substrate specificity. The N1 and N2 sialidase subtypes of the human influenza A virus had no significant variation in their substrate specificity for the gangliosides. Analysis of 11 synthetic gangliosides, which contained various ceramide or sialic acid moieties, demonstrated that A/Aichi/2/68 (H3N2) sialidase recognized the ceramide and sialic acid moiety and the length and structure of the sialyl sugar chain.
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PMID:Specificity of the N1 and N2 sialidase subtypes of human influenza A virus for natural and synthetic gangliosides. 959 19


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