Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.2.1.23 (beta-galactosidase)
 14,648 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The synthesis of glycoproteins containing N-linked complex oligosaccharides is blocked by swainsonine at the step catalyzed by Golgi mannosidase II (Tulsiani, D. R. P., Harris, T. M., and Touster, O. (1982) J. Biol Chem. 257, 7936-7939). Accordingly, hybrid glycoproteins might be produced in the presence of swainsonine. In this report, we demonstrate that swainsonine causes human skin fibroblasts to synthesize such glycoproteins. In control fibroblasts, there were approximately equal amounts of complex and high mannose glycoproteins. In the presence of swainsonine (10 micrograms/ml), most of the complex glycoproteins were replaced by hybrid types. The principal oligosaccharide had the following structure: (formula; see text) A smaller amount of the asialo hybrid was also produced. The structure of the hybrid was established by Bio-Gel P-4 fractionation of oligosaccharides produced by endoglycosidase H treatment of pronase-derived glycopeptides, followed by examination of the susceptibility of the oligosaccharide to glycohydrolases and by its adsorbability to serotonin-Sepharose 4B. The same hybrid oligosaccharide was produced efficiently by rat liver Golgi membranes in the presence of ([3H] Man)5GlcNAc, UDP-GlcNAc, UDP-Gal, CMP-NeuAc, and swainsonine. Golgi mannosidase II had no action on the hybrid oligosaccharide, and little action on asialo hybrid, but both were converted to the mannosidase II substrate, GlcNAcMan5GlcNAc, by appropriate treatment with neuraminidase and beta-galactosidase. Jack bean alpha-D-mannosidase gave the expected yields of free mannose from the various oligosaccharides studied in this work. Swainsonine should be useful in investigating the role of oligosaccharide structure of glycoproteins because of its ability to alter the oligosaccharide.
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PMID:Swainsonine causes the production of hybrid glycoproteins by human skin fibroblasts and rat liver Golgi preparations. 640 79

Swainsonine, an indolizidine alkaloid, inhibits the alpha-mannosidase that is involved in glycoprotein processing. Thus, in cultured animal cells, this alkaloid causes an increase in the surface content of high mannose glycoproteins and a decrease in the amount of complex type glycoproteins (Elbein, A. D., Solf, R., Dorling, P. R., and Vosbeck, K. (1982) Proc. Natl. Acad. Sci. U. S. A., 78, 7393-7397). In this report, the effect of swainsonine on the synthesis virus hemagglutinins was examined. Primary calf kidney cultures were infected with influenza virus and viral replication was allowed to proceed in the absence or presence of swainsonine. Several hours after the addition of swainsonine, [2-3H]mannose or [6-3H]glucosamine were added to label the hemagglutinins and the mature virus particles were isolated. Virus particles raised in the presence of this alkaloid had the same infectivity and hemagglutination titer as virus particles from control cells. However, when the hemagglutinins were examined on sodium dodecyl sulfate gels, the major hemagglutinin (HA0) and its subunits, HA1 and HA2, from swainsonine-treated cells, migrated faster, indicating that they were of lower molecular weights. The labeled hemagglutinins were digested with pronase and the resulting glycopeptides were chromatographed on Bio-Gel P-4. Both the mannose-labeled and glucosamine-labeled glycopeptides from swainsonine-treated virus migrated more slowly on these columns than those of controls cells, suggesting that they were altered in structure. Furthermore, when the glycopeptides were digested with endoglucosaminidase H, 90% of the glycopeptides from swainsonine-treated cells were susceptible to this enzyme, whereas only 30% of those from control cells were digested. The major oligosaccharide released from inhibited cells by endoglucosaminidase H was digestible with alpha-mannosidase, whereas that of control cells was resistant to this enzyme. However, the control cell glycopeptide was digested by a combination of neuraminidase, beta-galactosidase, beta-N-acetylhexosaminidase, and alpha-mannosidase. These data show that swainsonine prevents the formation of complex glycoproteins and gives rise to increased amounts of high-mannose glycoproteins.
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PMID:Swainsonine prevents the processing of the oligosaccharide chains of influenza virus hemagglutinin. 679 7