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:3.2.1.23 (beta-galactosidase)
14,648 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Fragment 1, released from bovine plasma high-molecular-weight kininogen by the action of plasma kallikrein, is a glycopeptide with approximately 3 mol of each of N-acetylgalactosamine, galactose and sialic acid in one molecule. All these sugars were in the T-1 fragment obtained by tryptic digestion of fragment 1. Sialic acid can be completely released from the T-1 fragment by sialidase digestion. When this sialic acid-free T-1 fragment was incubated with purified diplococcal endo-alpha-N-acetylgalactosaminidase, all remaining sugars were released as a disaccharide. By Smith degradation and beta-galactosidase digestion, the structure of this disaccharide was found to be Gal beta 1 leads to 3GalNAc. Methylation analysis of the trisaccharide released from fragment T-1 by alkaline borohydride treatment indicated that all the galactose was obtained as the 2,4,6-tri-O-methyl derivative. Based on this evidence, the complete structure of the carbohydrate moieties of fragment 1 was proposed as Sialyl alpha 2 leads to 3Gal beta 1 leads to 3GalNAc. In addition, small amounts of a tetrasaccharide, Sialyl alpha 2 leads to 3Gal beta 1 leads to 3(Sialyl alpha 2 leads to 6)GalNAc also occurred as a carbohydrate chain of fragment 1.
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PMID:The carbohydrate structure of a glycopeptide released by the action of plasma kallikrein on bovine plasma high-molecular-weight kininogen. 91 96

Sialic acid-containing carbohydrates were isolated from sialidosis urine by a combination of gel-filtration on Bio-Gel P-6 and medium-pressure anion-exchange chromatography on Mono Q. The Mono Q fractions were subjected to 500-MHz 1H-NMR spectroscopy, sugar analysis and analytical HPLC on Lichrosorb-NH2. These methods indicated the presence of various N-acetyllactosamine type sialyloligosaccharides differing from each other in branching pattern and sialic acid linkage types. Among the structures were fully and partially sialylated mono-, di-, tri- and tetra-antennary compounds. A comparison with the results from galactosialidosis urine indicated that essentially the same carbohydrates were present in both urines, but that the relative amounts of the various sialyloligosaccharides differ to some extent. Sialidosis urinary oligosaccharides contained relatively more alpha 2-6 linked sialic acid than oligosaccharides from galactosialidosis urine. It could be concluded that the additional beta-galactosidase deficiency in galactosialidosis did not influence the nature of the excreted material and that the sialidase deficiency determined completely the defective catabolism of glycoproteins in both sialidosis and galactosialidosis.
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PMID:A comparative study of sialyloligosaccharides isolated from sialidosis and galactosialidosis urine. 177 19

The subcellular distribution of sialyltransferase and its product of action, sialic acid, was investigated in the undifferentiated cells of the rat intestinal crypts and compared with the pattern observed in the differentiated cells present in the surface epithelium. Sialyltransferase was immunocytochemically detected with an antibody, affinity-purified on a beta-galactosidase/sialyltransferase fusion protein, which recognizes only protein epitopes of the enzyme. A similar pattern and intensity of immunolabeling were observed in the Golgi apparatus, apical and basolateral plasma membranes of both undifferentiated and differentiated absorptive cells. However, in the goblet cells, the mucus was only weakly labeled in cells present in the basal portion of the crypts but increased in intensity through the zone of migration to the surface epithelium. Sialic acid as detected with the Limax flavus lectin was observed in the Golgi apparatus and post-Golgi apparatus structures of both absorptive and goblet cells regardless of their position along the crypt-to-surface epithelium axis. However, a striking difference in the plasma membrane distribution of sialic acid existed between undifferentiated cells of the lower half of the crypts and those of the upper half and the surface epithelium: in the former, label was present in both the apical and basolateral domain, whereas in the latter it became restricted to the apical domain. These results suggest that the presence of sialyltransferase immunoreactivity in the goblet cell mucus and the polarization of sialic acid to the apical plasma membrane of both goblet and absorptive cells may be markers for the differentiated state.
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PMID:Alteration in sialyltransferase and sialic acid expression accompanies cell differentiation in rat intestine. 245 28

In this study we further define cell surface carbohydrate structures relevant to cellular interactions that regulate erythropoiesis. An analysis of thymocyte cell surface negativity was made using fluoresceinated poly-L-ornithine (FITC poly-L-ornithine) as a probe that binds to negatively charged sites (i.e., sialic acid residues) at the cell surface. Two distinct subpopulations are labeled, comprising both intensely as well as weakly fluorescent subpopulations of thymocytes. Prior treatment of thymocytes with Vibrio cholerae neuraminidase (VCN), which removes cell surface sialic acid residues, markedly reduced the FITC poly-L-ornithine surface labeling of these cells. Distinct enzymatic modifications of regulatory cell functions were also assessed by the ability of thymocytes to function as separate regulatory subpopulations. Confirming our previous observations, treating thymocytes with VCN impaired the enhancement activity but had little effect on thymocyte regulatory ability to suppress erythroid colony growth. In contrast, treatment of thymocytes with galactose oxidase (GAO) or beta-galactosidase (beta-GAL) removed suppressor activity either before or after VCN treatment. A further exposure of GAO-treated thymocytes to sodium borohydride or hydroxylamine, which reduce D-galactose residues, restores their suppressor function and prevents enhancement. These differential enzymatic effects on thymocyte regulatory cell functions suggest that different carbohydrate structures may be involved in helper and suppressor activities for erythroid colony formation. Sialic acid residues may be associated with certain cells that function to enhance erythropoiesis, and D-galactose residues may be associated with the suppressor subpopulation.
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PMID:Effects of neuraminidase on the regulation of erythropoiesis: III: Characterization of carbohydrate moieties on the surface of thymic regulatory cells that interact with erythroid colony-forming cells. 256 44

Sites of binding of eight different lectins (LTA, UEA I, WGA, SBA, DBA, CON A, PNA, RCA I) to cat submandibular gland were studied after exposure of tissue sections to sialidase, alpha-fucosidase, beta-galactosidase, alpha-mannosidase, beta-N-acetylglucosaminidase. All lectins were affected by enzymatic predigestion and the labeling of individual lectins was highly dependent upon the glycosidase used to pretreat the sections. Glycoconjugates of demilunar, acinar and ductal cells exhibited a different composition of terminal sequences. For example, fucose proved to form the disaccharide fucose-galactose in demilunar and acinar cells, whereas it was present with the sequence fucose-N-acetyl-D-glucosamine in striated duct cells. Sialic acid participated both to the terminal sequence sialic acid-galactose and sialic acid-N-acetyl-D-galactosamine either in demilunar or in ductal cells. Lectin labeling combined with glycosidase digestion was also helpful in verifying the influence of neighbouring oligosaccharides on the affinity of lectins for the respective sugars.
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PMID:Enzymatic degradation and quantitative lectin labeling for characterizing glycoconjugates which act as lectin acceptors in cat submandibular gland. 271 45

Sialic acid-containing storage material was isolated from cultured human galactosialidosis fibroblasts, by a combination of gel filtration and anion-exchange chromatography on Mono Q. The obtained sialyloligosaccharides were analyzed by 500-MHz 1H-NMR spectroscopy in combination with sugar analysis and analytical HPLC. The storage material consisted of a series of completely sialylated N-acetyl-lactosamine type of structures having Man beta 1-4GlcNAc at the reducing terminus in common, similar to those recently reported for human sialidosis fibroblasts. Comparison of the storage material from both sources revealed only differences in their relative amounts. In control fibroblasts these compounds could not be detected. The nature of the accumulated compounds is in accordance with the alpha-neuraminidase deficiency in both genetic diseases. The additional deficiency of beta-galactosidase in case of galactosialidosis is not reflected in the storage material.
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PMID:A comparative study of the accumulated sialic acid-containing oligosaccharides from cultured human galactosialidosis and sialidosis fibroblasts. 313 48

The MAT-B1 and MAT-C1 ascites sublines of the 13762 rat mammary adenocarcinoma, which differ in several cell surface properties, contain a major mucin-type glycoprotein, termed ASGP-1. The sialic acid content of MAT-C1 ASGP-1 is 2-3-fold greater than MAT-B1 ASGP-1 (Sherblom, A. P., Buck, R. L., and Carraway, K. L. (1980) J. Biol. Chem. 255, 783-790). Sialic acid analysis demonstrated that, whereas MAT-C1 ASGP-1 contained approximately equal amounts of N-acetylneuraminic acid (NeuAc) and N-glycolylneuraminic acid (NeuGl), MAT-B1 ASGP-1 was devoid of NeuGl. MAT-B1 microsomes also did not contain NeuGl. MAT-B1 cells incubated with [3H]N-acetylmannosamine did not synthesize either labeled CMP-NeuGl or free NeuGl, even though the CMP-sialic acid synthetase was active with the substrate NeuGl. Thus, MAT-B1 cells may be deficient in the enzyme N-acetylneuraminate monooxygenase. The O-linked oligosaccharides from both MAT-B1 and MAT-C1 ASGP-1 have been shown to contain a core tetrasaccharide Gal(beta 1-4)GlcNAc(beta 1-6)(Gal(beta 1-3]GalNAc in which both galactose residues may be linked to additional sugars (Hull, S. R., Laine, R. A., Kaizu, T., Rodriquez, I., and Carraway, K. L. (1984) J. Biol. Chem. 259, 4866-4877). The distribution of NeuAc and NeuGl between the two galactose termini of the core tetrasaccharide was examined for MAT-C1 ASGP-1. Oligosaccharides were released by alkaline-borohydride treatment of MAT-C1 ASGP-1 which had been labeled with [14C]glucosamine and galactose oxidase/B3H4. Following fractionation by Bio-Gel P-4, DEAE-Sephadex, and high-performance liquid chromatography, oligosaccharides were analyzed for NeuAc and NeuGl and for susceptibility to digestion with beta-galactosidase. Three disialylated oligosaccharides were identified containing 2 mol of NeuAc (5.5% recovery), 2 mol of NeuGl (4.5%), or 1 mol each of NeuAc and NeuGl (11.1%). For monosialylated oligosaccharides, NeuGl appeared preferentially associated with the Gal(beta 1-4)GlcNAc terminus (9.0%), whereas significant amounts of oligosaccharide containing NeuAc at both the Gal(beta 1-3)GalNAc (2.6%) and Gal(beta 1-4)GlcNAc (4.5%) termini were detected. Each of the major qualitative differences between MAT-B1 and MAT-C1 oligosaccharides, including the presence of NeuGl (MAT-C1), sulfate (MAT-B1), and alpha-linked galactose (MAT-B1), occurs at the Gal(beta 1-4)GlcNAc terminus.
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PMID:N-Acetylneuraminic acid and N-glycolylneuraminic acid in the O-linked oligosaccharides of a tumor cell glycoprotein. Incorporation and distribution. 391 40

An adult case of mucolipidosis with beta-galactosidase and neuraminidase deficiencies is reported. The patient was a 35-year-old Japanese female with coarse face, lumbar vertebral beaking, action myoclonus, cerebellar ataxia, clouding of the cornea, macular cherry-red spots, hearing loss and vacuolated lymphocytes, but without mucopolysacchariduria. Her clinical symptoms developed at a late age with a slow progression. The enzyme activities of beta-galactosidase were deficient in leukocytes and cultured skin fibroblasts but normal in serum. Sialic acid-rich glycopeptides and oligosaccharides were increased in the urine. Neuraminidase activities toward fetuin, alpha-N-acetylneuraminosyl-(2 leads to 3) lactose and alpha-N-acetylneuraminosyl-(2 leads to 6) lactose were deficient in cultured fibroblasts. It is suggested that the main disturbance in the present case might be the catabolic process of glycoproteins and oligosaccharides due to neuraminidase deficiency.
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PMID:Adult mucolipidosis with beta-galactosidase and neuraminidase deficiencies. 677 51

Sialic acid is the receptor determinant for the human parainfluenza virus type 3 (HPF3) hemagglutinin-neuraminidase (HN) glycoprotein, the molecule responsible for binding of the virus to cell surfaces. In order for the fusion protein (F) of HPF3 to promote membrane fusion, HN must interact with its receptor. In addition to its role in receptor binding and fusion promotion, the HPF3 HN molecule contains receptor-destroying (sialidase) activity. The putative active sites are in the extracellular domain of this type II integral membrane protein. However, HN is not available in crystalline form; the exact locations of these sites, and the structural requirements for binding to the cellular receptor, which has not yet been isolated, are unknown. Nor have small molecular synthetic inhibitors of attachment or fusion that would provide insight into these processes been identified. The strategy in the present study was to develop an assay system that would provide a measure of a specific step in the viral cycle-functional interaction between viral glycoproteins and the cell during attachment and fusion-and serve to screen a variety of substances for inhibitory potential. The assay is based on our previous finding that CV-1 cells persistently infected (p.i.) with HPF3 do not fuse with one another but that the addition of uninfected CV-1 cells, supplying the critical sialic acid containing receptor molecules that bind HN, results in rapid fusion. In the present assay two HeLa cell types were used: we persistently infected HeLa-LTR-betagal cells, assessed their fusion with uninfected HeLa-tat cells, and then quantitated the beta-galactosidase (betagal) produced as a result of this fusion. The analog alpha-2-S-methyl-5-N-thioacetylneuraminic acid (alpha-Neu5thioAc2SMe) interfered with fusion, decreasing betagal production by 84% at 50 mM and by 24% at 25 mM. In beginning to extend our studies to different types of molecules, we tested an unsaturated derivative of sialic acid, 2,3-dehydro-2-deoxy-n-acetyl neuraminic acid (DANA), which is known to inhibit influenza neuraminidase by virtue of being a transition-state analog. We found that 10 mM DANA inhibited neuraminidase activity in HPF3 viral preparations. More significantly, this compound was active in our assay of HN-receptor interaction; 10 mM DANA completely blocked fusion and betagal production, and hemadsorption inhibition by DANA suggested that DANA blocks attachment. In plaque reduction assays performed with the compounds, the active analog alpha-Neu5thioAc2SMe reduced plaque formation by 50% at a 50 mM concentration; DANA caused a 90% inhibition in the plaque reduction assay at a concentration of 25 mM. Our results indicate that specific sialic acid analogs that mimic the cellular receptor determinant of HPF3 can block virus cell interaction and that an unsaturated n-acetyl-neuraminic acid derivative with affinity to the HN site responsible for neuraminidase activity also interferes with HN-receptor binding. Strategies suggested by these findings are now being pursued to obtain information regarding the relative locations of the active sites of HN and to further elucidate the relationship between the receptor-binding and receptor-destroying activities of HN during the viral life cycle. The quantitative assay that we describe is of immediate applicability to large-scale screening for potential inhibitors of HPF3 infection in vivo.
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PMID:The use of a quantitative fusion assay to evaluate HN-receptor interaction for human parainfluenza virus type 3. 1060 17

This review summarizes the current research on human exo-alpha-sialidase (sialidase, neuraminidase). Where appropriate, the properties of viral, bacterial, and human sialidases have been compared. Sialic acids are implicated in diverse physiological processes. Sialidases, as enzymes acting upon sialic acids, assume importance as well. Sialidases hydrolyze the terminal, non-reducing, sialic acid linkage in glycoproteins, glycolipids, gangliosides, polysaccharides, and synthetic molecules. Therefore, a variety of assays are available to measure sialidase activity. Human sialidase is present in several organs and cells. Its cellular distribution could be cytosolic, lysosomal, or in the membrane. Human sialidase occurs in a high molecular-mass complex with several other proteins, including cathepsin A and beta-galactosidase. Multi-protein complexation is important for the in vivo integrity and catalytic activity of the sialidase. However, multi-protein complexation, the occurrence of isoenzymes, diverse subcellular localization, thermal instability, and membrane association have all contributed to difficulties in purifying and characterizing human sialidases. Human sialidase isoenzymes have recently been cloned and sequenced. Even though crystal structures for the human sialidases are not available, the highly conserved regions of the sialidase from various organisms have facilitated molecular modeling of the human enzyme and raise interesting evolutionary questions. While the molecular mechanisms vary, genetic defects leading to human sialidase deficiency are closely associated with at least two well-known human diseases, namely sialidosis and galactosialidosis. No therapy is currently available for either disease. A thorough investigation of human sialidases is therefore crucial to human health.
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PMID:Comparative enzymology, biochemistry and pathophysiology of human exo-alpha-sialidases (neuraminidases). 1133 49


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