Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

Sialic acids and sialidases play important roles in cellular interactions and modulate the recognition of pathogenic microbes by mammalian host cells. Protozoan parasites of the genus Trypanosoma express a unique sialic acid-metabolizing enzyme. This enzyme, named trans-sialidase (TS), catalyzes the transfer of sialic acids from host glycoconjugates to acceptor molecules of the parasite plasma membrane. In African trypanosomes, the agents of sleeping sickness, TS is found only in forms developing within the insect vector, and the enzyme sialylates the major surface protein. In Trypanosoma cruzi, the causative agent of Chagas' disease in Central and South America, TS is expressed both in the insect and mammalian forms of the parasite. The T. cruzi enzyme has been biochemically characterized, and the gene encoding the enzyme has been cloned. The enzyme sialylates abundant mucin-like molecules present on the surface of the parasite. Several lines of evidence suggest that TS and sialic acid acceptors on the surface of T. cruzi participate in host-parasite interactions and mediate the initial stages of the trypanosomes' invasion of host cells.
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PMID:Structural and functional properties of Trypanosoma trans-sialidase. 782 16

The mucin-type carbohydrate Tn cryptantigen (GalNAc alpha 1-O-Ser/Thr, where GalNAc is N-acetyl-D-galactosamine) is expressed in many carcinomas, in haemopoietic disorders including the Tn syndrome, and on human immunodeficiency virus (HIV) coat glycoproteins, but is not expressed on normal, differentiated cells because of the expression of a Tn-processing galactosyltransferase. Using Jurkat T leukaemic cells which express high levels of Tn antigen due to deficient Tn galactosylation, we have established the Tn antigen-mediated gene transfer and demonstrate the considerable efficiency of this approach. We used poly(L-lysine) conjugates of the monoclonal antibody 1E3 directed against the Tn antigen to deliver the luciferase and beta-galactosidase reporter genes to Jurkat cells by receptor-mediated endocytosis. Addition of unconjugated 1E3 reduced transfection efficiency in a concentration-dependent manner and incubation with free GalNAc abolished DNA transfer completely, indicating that gene delivery is indeed mediated by the Tn antigen. Pre-treatment of Jurkat cells with Vibrio cholerae sialidase, which uncovers additional Tn antigens, resulted in an improvement of gene transfection. Both human and chicken adenovirus particles attached to the DNA/polylysine complex strongly augmented transgene expression. When the beta-galactosidase (lacZ) gene was delivered to Jurkat cells by Tn-mediated endocytosis, up to 60% of the cells were positive in the cytochemical stain using 5-bromo-4-chloro-3-indolyl-beta-D-galactopyranoside (X-gal) as a chromogenic substrate. The efficiency of the transferrin receptor-mediated DNA uptake into Jurkat cells was comparatively low, although these cells were shown to express considerable amounts of transferrin receptor. We show here that a mucin-type carbohydrate antigen mediates highly efficient DNA uptake by endocytosis into Jurkat T cells. This method represents a 50-fold improvement of Jurkat cell transfection efficiency over other physical gene transfer techniques. Specific gene delivery to primary cancer cells exhibiting Tn epitopes may especially be desirable in immunotherapy protocols.
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PMID:Carbohydrate receptor-mediated gene transfer to human T leukaemic cells. 782 4

An isolate of Streptococcus intermedius from a brain abscess showed neuraminidase (sialidase), beta-D-galactosidase, N-acetyl-beta-D-glucosaminidase and N-acetyl-beta-D-galactosaminidase activities. The optimal pH values of these enzymes were 5.5-6.0, 5.5-6.0, 5.0-5.5 and 5.0-5.5, respectively. The km of the enzymes varied according to whether the type of substrate was chromogenic or fluorogenic; sialidase was most active at the lowest substrate concentrations, with a km of 0.01 mM. In semi-defined medium, with porcine gastric mucin--a model glycoprotein--as the sole source of fermentable carbohydrate, levels of the glycosidases were significantly increased. Addition of glucose to the mucin-containing medium, or growth of cells in media supplemented with glucose alone, repressed glycosidic activities and the majority of these were cell-associated. S. intermedius cells from cultures grown with mucin were able, simultaneously, to transport via sugar:phosphoenolpyruvate phosphotransferase (PTS) systems, monosaccharides which are constituents of carbohydrate side chains of glycoproteins. These cells also possessed significant levels of neuraminate-pyruvate lyase, involved in the intracellular catabolism of neuraminic acid; this was absent from cells grown with glucose. These mechanisms, collectively, may facilitate the persistence and growth of S. intermedius in vivo.
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PMID:Production of specific glycosidase activities by Streptococcus intermedius strain UNS35 grown in the presence of mucin. 806 38

Trans-sialidase catalyzes the transference of sialic acid from host to the Trypanosoma cruzi surface. Here, we characterize the sialic acid acceptors of this protozoan parasite as mucin-like molecules, which are anchored to the membrane by glycosylphosphatidylinositol. The mucins isolated from the insect stages differ from the mucins isolated from the mammalian stages in size and reactivity to monoclonal antibodies, suggesting that they are formed by variable polypeptide chains and/or O-linked carbohydrate structures.
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PMID:Sialic acid acceptors of different stages of Trypanosoma cruzi are mucin-like glycoproteins linked to the parasite membrane by GPI anchors. 808 Dec 62

The target molecules on the cell surface of Trypanosoma cruzi trypomastigotes reacting with lytic anti-alpha-galactosyl antibodies from chronic patients with Chagas' disease (Ch anti-Gal) have been purified by solvent extraction and identified as glycoconjugates migrating in the 74-96-kDa range (F2 antigen) and in the 120-200-kDa range (F3 antigen) on SDS-PAGE. The F3 antigen was tested for binding to Ch and normal human serum (NHS) anti-Gal and to MoAb 3C9. We observed that Ch anti-Gal and MoAb 3C9, but not NHS anti-Gal, bind strongly to the trypomastigote glycoconjugates. These antibodies, however, did not compete with each other for binding to F3 molecules, indicating that they are recognizing different epitopes. Binding of Ch anti-Gal to F3 antigen is abolished by treatment of these molecules with alpha- but not beta-galactosidase. Binding of 3C9 MoAb is abolished by treatment of F3 with sialidase. F2/F3 antigens absorbed Ch anti-Gal as well as lytic antibodies from total chagasic sera. These antigens also specifically discriminate between the serum reactivity of patients with active Chagas' disease and those of sera from cured patients, drug-treated patients with dissociated serology (positive conventional serology, negative trypanolytic activity), healthy individuals, and patients with several other infectious diseases. We also observed that F2/F3 antigens are anchored to the parasite membrane via glycosylphosphatidylinositol (GPI). The alpha-galactosyl epitopes recognized by Ch anti-Gal are present in a series of O-linked oligosaccharide chains in the mucin-like glycoprotein component of the complex.
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PMID:GPI-anchored glycoconjugates from Trypanosoma cruzi trypomastigotes are recognized by lytic anti-alpha-galactosyl antibodies isolated from patients with chronic Chagas' disease. 808 Dec 63

During invasion of multicellular organisms, protozoan parasites expose functional molecules that become targets for the host immune response. Recent research on Trypanosoma cruzi, the agent of Chagas' disease, suggests a new model of how the parasite might deal with this problem. Several antigens of T. cruzi have tandemly repeated amino acid motifs in molecules with as yet unknown functions. In two cases, these repeats are in molecules with a defined structure or function. Both proteins are implicated in the invasion of host-cells by the parasite. One of these is the core protein of a putative mucin-like glycoprotein that has Thr/Pro-rich repeats which, by themselves, might define the structure of a highly O-glycosylated molecule. The other protein is SAPA/trans-sialidase/neuraminidase, a molecule able to transfer sialic acid, that has so far only been described in trypanosomes. The amino acid repeats present in SAPA/transsialidase/neuraminidase are unrelated to the enzymic activity and constitute an immunodominant C-terminal domain. The N-terminal domain of SAPA/trans-sialidase/neuraminidase controls the enzymic activity since a recombinant molecule lacking the repeats conserves trans-sialidase activity. That both domains are functionally independent is also indicated by experiments that show that antibodies directed against the amino acid repeats are unable to inhibit trans-sialidase activity. A large number of proteins having trans-sialidase related sequences but lacking enzymic activity are also present in the surface membrane of the parasite. The immunodominant SAPA/trans-sialidase/neuraminidase repeats, together with the complex network of cross-reacting epitopes present in related but enzymatically inactive proteins might contribute to the delay in mounting an effective antibody response.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Trans-sialidase, SAPA amino acid repeats and the relationship between Trypanosoma cruzi and the mammalian host. 808 53

A sample of 219 primary stomach cancers, 143 advanced cancers and 76 early cancers were examined for mucin histochemical staining (the paradoxical concanavalin A method, the galactose oxidase-Schiff [GOS] reaction, and the sialidase-GOS reaction) and immunohistochemical reactivity (pepsinogen [Pg] I, Pg II, SH-9 and TKH-2). Gastric cancer cells were clearly classified according to mucin histochemistry into a gastric type, including mucus neck cell, pyloric gland cell and surface mucus cell types, and an intestinal type, including goblet-cell, and intestinal absorptive cell types. TKH-2 monoclonal antibody, which recognizes the mucin-associated sialosyl-Tn antigen, reacted with the mucin of goblet cells in both the normal small intestine and in the intestinal metaplasia of the stomach. Sixty-five of 106 (61%) differentiated adenocarcinomas and 76 of 113 (67%) undifferentiated adenocarcinomas had over 10% of their cancer cells positive for TKH-2. The TKH-2-positive cancers were primarily classified as a goblet-cell type by mucin-histochemical staining and the other immunohistochemical staining methods. Therefore, it is concluded that sialosyl-Tn is an excellent marker of small intestinal mucins and is indicative of a small intestinal type of differentiation in two-thirds of gastric cancers.
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PMID:Expression of sialosyl-Tn in intestinal type cancer cells of human gastric cancers. 831 Aug 25

The natural sialidase of Clostridium septicum was purified and characterized in parallel with the recombinant enzyme expressed by Escherichia coli. The two enzymes exhibit almost identical properties. The maximum hydrolytic activity was measured at 37 degrees C in 60 mM sodium acetate buffer, pH 5.3. Glycoproteins like fetuin and saponified bovine submandibular gland mucin, most of them having alpha(2-6) linked sialic acids, are preferred substrates, while sialic acids from gangliosides, sialyllactoses, or the alpha(2-8) linked sialic acid polymer (colominic acid) are hydrolysed at lower rates. alpha(2-3) Linkages are more rapidly hydrolysed than alpha(2-6) bonds of sialyllactoses. The cleavage rate is markedly reduced by O-acetylation of the sialic acid moiety. These properties are similar to those of other secreted clostridial sialidases. The enzyme exists in mono-, di- and trimeric forms, the monomer exhibiting a molecular mass of 125 kDa, which is close to the protein mass of 111 kDa deduced from the nucleotide sequence of the cloned gene.
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PMID:Isolation and properties of the natural and the recombinant sialidase from Clostridium septicum NC 0054714. 835 27

Sporozoites and merozoites of three species of Eimeria, E. tenella, E. maxima, and E. necatrix, that cause diarrhea in chickens worldwide, were examined for their expression of sialidase (SA) activity. The enzyme was found in three species, and the activity of merozoites was 10-20 times higher than that of sporozoites. The enzyme was resistant to degradation by proteases that are normally present in the intestine, a site inhabited by the Eimeria parasites, and it was relatively resistant to heat, with optimum activity being at 40 degrees C, which is within the range of temperature in the chicken intestine (40-43 degrees C). E. tenella SA was immunoprecipitated by monoclonal and polyclonal antibodies raised against the Trypanosoma cruzi SA (TCSA), and enzyme activity was neutralized by these antibodies. E. tenella SA was identified by immunoblots as a doublet of molecular weight 190,000 and 180,000 using, as a probe, anti-TCSA antibodies and antibodies against a synthetic peptide (TR) derived from the long tandem repeat domain of TCSA. Binding of the monoclonal and polyclonal antibodies to E. tenella was completely blocked by TR, but not by an irrelevant peptide (BR). Therefore, E. tenella expresses a developmentally regulated SA that is structurally related to the T. cruzi counterpart. Because of the high SA activity in merozoites, and by analogy with other SA-producing microbes that inhabit mucin-rich epithelia, we suggest that the Eimeria SA plays a role in desialylating intestinal mucins to reduce viscosity of the local environment and thereby facilitate parasite migration. The enzyme could also play a role in host cell-parasite interaction.
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PMID:Identification of a developmentally regulated sialidase in Eimeria tenella that is immunologically related to the Trypanosoma cruzi enzyme. 835 28

Sialidase activity in normal faecal extracts showed a preference for mucin-related glycoprotein and oligosaccharide substrates, but the presence of two or more O-acetyl esters at positions C7-C9 on the sialic acids retarded the rate of hydrolysis. A specific sialate O-acetyl esterase was detected with a lower total activity relative to sialidase with mucin substrates and having a pH optimum of 7.8 and a KM of approximately 1 mM sialate O-acetyl ester. A specific glycosulfatase activity was found in faecal extracts using the substrate lactit-[3H]ol 6-O-sulfate with a pH optimum of pH 5.0 and a KM of approximately 1 mM. Faecal extracts from ulcerative colitis (UC) patients had higher sialate O-acetyl esterase and glycosulfatase activity, while mucin sialidase activity was unchanged. Metabolically labelled mucin isolated from UC patients contained less sulfate and had lower sialic acid O-acetylation compared with normal mucin. Colonic mucin was degraded more efficiently by faecal extracts from UC patients compared with normal extracts. The UC mucin was degraded more rapidly than the normal mucin by faecal enzyme extracts from both normal and UC subjects.
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PMID:The roles of enteric bacterial sialidase, sialate O-acetyl esterase and glycosulfatase in the degradation of human colonic mucin. 835 29


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