Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.4.99.6 (sialyltransferase)
 1,546 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

High field magnetic resonance spectroscopy has been utilized to deduce the primary structure of the glycopeptides from a human myeloma gamma 1-immunoglobulin G (Tem). The major structures found belong to the biantennary complex class of glycopeptides, with a minor (5%) fraction belonging to the bisected biantennary complex class. In the biantennary class, three structures were present with different residues at the termini of the alpha Man(1-6) and alpha Man(1-3) arms: (i) with beta Gal(1-4) and alpha NeuNAc(2-6), respectively (33%); (ii) with beta Gal(1-4) and beta Gal(1-4), respectively (45%); and (iii) beta Gal(1-4) and beta GlcNAc(1-2), respectively (17%). In the bisected biantennary class only the latter termini were found for the two arms. These results suggest that the galactosyl transferase in these cells has a preference for the beta GlcNAc(1-2) of the alpha Man(1-6) arm and that the sialyltransferase has a preference for the beta Gal(1-4) of the alpha Man(1-3) arm.
Can J Biochem 1982 Dec
PMID:Structure of the glycopeptides of a human gamma 1-immunoglobulin G (Tem) myeloma protein as determined by 360-megahertz nuclear magnetic resonance spectroscopy. 716 34

A sialyltransferase enzyme, present in the microsomal fraction of mouse brain, catalyzes the synthesis in vitro of a lipid, characterized as 1,2-diacyl-3-beta-D-galactosyl (3 comes from 2 N-acetylneuraminosyl)-sn-glycerol, (sialosylgalactosyldiacylglycerol) from 1,2-diacyl-3-beta-D-galactosyl-sn-glycerol (galactosyldiacylglycerol) and cytidine-5'-monophospho-N-acetylneuraminic acid (CMP-NeuNAc). The enzymatic activity increases proportionally, over a given range, with increasing concentrations of both substrates and of enzyme. The apparent Km of the enzyme for galactosyldiacylglycerol is 130 microM, and for CMP-NeuNAc, 780 microM. The reaction proceeds optimally at pH 6.2. The product of the enzymatic reaction was characterized as a lipid which contained galactosyldiacylglycerol and N-acetylneuraminic acid. 14C-labeled lipid, synthesized from [14C]N-acetylneuraminic acid, and 3H-labeled lipid, synthesized from [3H]galactosyldiacylglycerol, ran with identical RF values when chromatographed on thin layers of silica gel. The water-soluble products, obtained by mild alkaline deacylation of these two labeled lipids, migrated the same when electrophoresed on paper. The ratio 14C/3H was calculated as 0.83 for doubly labeled lipid, [14C]sialosyl-[3H]galactosyldiacylglycerol. Degradation of this doubly labeled lipid by mild alkaline deacylation, followed by mild acid hydrolysis, yielded products that cochromatographed with standards galactosylglycerol and N-acetylneuraminic acid. Analysis of the products resulting from periodate oxidation of the 3H-labeled lipid demonstrated that the N-acetylneuraminic acid is linked to carbon 3 of the galactose.
J Biol Chem 1981 Dec 10
PMID:Biosynthesis in vitro of sialosylgalactosyldiacylglycerol by mouse brain microsomes. 729 58

Total labeled glycolipids from thymocytes of leukemic AKR/J mouse thymus incubated for 24 h in the presence of the precursors [3H] galactose or [14C] glucosamine were found to exceed those from non-leukemic thymocytes. The amount of labeled compounds that co-migrated with monosialogangliosides (GM3 and GM2) and disialogangliosides (GD1a and GD1b) was higher, whereas incorporation into monosialoganglioside (GM1) and trisialoganglioside (GT1) was lower in leukemic than in non-leukemic thymocytes. Consistent with this altered pattern of ganglioside distribution was the finding of a higher activity of two of the sialyltransferase activities in homogenates of leukemic thymus as compared to normal thymus. About 2-fold higher activities of the enzymes CMP-AcNeu: lactosylceramide sialyltransferase and CMP-AcNeu: GM1 sialyltransferase were observed in leukemic thymus homogenate compared to homogenates of non-leukemic cells. The substrate affinity of sialyltransferase with GM1 as acceptor from the leukemic thymus was similar to that of the enzyme from normal thymus. Thus, our studies reveal an enzymatic basis for the enhanced rate of synthesis and altered ganglioside profile observed in malignant thymocytes, and are consistent with the general view on the pattern of acidic glycolipids in tumorigenesis.
Biochim Biophys Acta 1981 Dec 04
PMID:Glycolipid sialyltransferases in normal and neoplastic murine thymocytes. 731 48

In searching for the gonococcal sialyltransferase gene(s), we cloned a 3.8-kb DNA fragment from gonococcus strain MS11 that hybridized with the oligonucleotide JU07, which was derived from the conserved C terminus of the sialyl motif present in mammalian sialyltransferases. Sequencing of the fragment revealed four putative open reading frames (ORFs), one of which (ORF-1) contained a partial sialyl motif including the amino acid sequence VGSKT, which is highly conserved among sialyltransferases. The gene was flanked by two inverted repeats containing the neisserial DNA uptake sequence and was preceded by a putative sigma 54 promoter. Database searches, however, revealed a high degree of homology between ORF-1 and the N-acetylglucosamine 1-phosphate uridyltransferase (GlmU) of Escherichia coli and Bacillus subtilis and not with any known sialyltransferase. This homology was further established by the successful complementation of an orf-1 mutation by the E. coli glmU gene. Enzyme assays demonstrated that ORF-1 did not possess sialyltransferase activity but mimicked GlmU function catalyzing the conversion of N-acetylglucosamine 1-phosphate into UDP-N-acetylglucosamine, which is a key metabolite in the syntheses of lipopolysaccharide, peptidoglycan, and sialic acids.
J Bacteriol 1995 Dec
PMID:Identification of the gonococcal glmU gene encoding the enzyme N-acetylglucosamine 1-phosphate uridyltransferase involved in the synthesis of UDP-GlcNAc. 759 84

There are various approaches for improving endoradiotherapy and diagnosis with monoclonal antibodies in nuclear medicine. The known methods of site-specific labelling of biomolecules based either on reactions with sulfhydryl groups or on reactions with aldehyde groups of the oligosaccharide chains effect unwanted alterations of the biomolecules. We present a new method to introduce radioactive halogens into the oligosaccharide chains of an antibody, based on the enzymatic transfer of the labelled synthetic sialic acid derivative CMP-9-deoxy-9-salizoyl-NeuAc. It was first labelled by the iodogen-method (iodine) in yields of more than 90%. Under selected conditions it was possible to obtain di- and trihalogenated products. Then the radioactive sialic acid derivatives were transferred during 90 minutes at room temperature with 2.6-sialyltransferase from rat liver into the oligosaccharide chains of antibodies. It is necessary to use neuraminidase pretreated antibodies with an increased number of binding sites for sialic acid derivatives. Yields of about 55% were obtained for the monoiodinated sialic acid derivative. With this method we present a reasonable alternative reaction of labelled compounds with biomolecules. Studies of the immunoreactivity are now in progress.
J Nucl Biol Med 1994 Dec
PMID:A new method for site-specific labelling of the oligosaccharide chain of antibodies: preliminary results. 763 60

Human colon cancer is associated with antigenic and structural changes in mucin-type carbohydrate chains (O-glycans). To elucidate the control of the biosynthesis of these O-glycans is colon cancer, we have studied glycosyltransferase and sulphotransferase activities involved in the assembly of elongated O-glycan structures. We analysed homogenates prepared from cancer tissue, adjacent normal and distal normal tissue from 20 patients. Several transferase activities showed pronounced changes in cancer tissue. The changes correlate with previous findings of a loss of O-glycans in cancer mucins, but did not always correlate with levels of Tn, sialyl-Tn, T and Lex antigens in homogenates or with the differentiation status and Duke's stages of the cancer tissue or the patient's blood type, sex and age. UDP-GlcNAc: Gal NAc-R beta 3-N-acetylglucosaminyltransferase (where GlcNAc is N-acetyl-D-glucosamine and GalNAc is N-acetyl-D-galactosamine) synthesizing O-glycan core 3, GlcNAc beta 1-3GalNAc-, CMP-sialic acid: GalNAc-peptide alpha 6-sialyltransferase synthesizing the sialyl-Tn antigen and sulphotransferase activities towards O-glycan core 1, Gal beta 1-3GalNAc-, were found to be decreased in cancer. UDP-GlcNAc: Gal beta 1-3GalNAc beta 6-N-acetylglucosaminyltransferase was also decreased in cancer concomitant with a loss of the ability to synthesize the I antigen and core 4, GlcNAc beta 1-6(GlcNAc beta 1-3) GalNAc-, CMP-sialic acid: Gal beta 1-3GalNAc-R alpha 3-sialyltransferase and GDP-fucose: Gal beta-R alpha 2-fucosyltransferase, synthesizing the blood group H determinant, were found to be 4- and 3- to 8-fold increased, respectively, in cancer compared to normal tissue. The data suggest that the biosynthesis of antigens and mucin-bound O-glycan structures in colon cancer is subject to complex control mechanisms.
Glycobiology 1994 Dec
PMID:Alterations of O-glycan biosynthesis in human colon cancer tissues. 773 50

CMP-N-acetylneuraminic acid:lactosylceramide (alpha 2-3) sialyltransferase (GM3-synthase) was purified to homogeneity from a Triton CF-54 extract of young rat brain. The enzyme was separated by affinity chromatography on CDP-Sepharose column and resolved by linear NaCl gradient elution from the same adsorbent. Final purification of GM3-synthase was achieved by chromatography on a "lactosylceramide acid"-Sepharose column and specific elution with lactosylceramide. The enzyme activity was highest at pH 6.5 and required the presence of Triton CF-54 (0.15%) and Mn2+ (10 mM) for its full activity. The product of the reaction catalyzed by the enzyme was identified as GM3 based on its mobility on thin layer chromatographic plates using two different solvent systems. Comparison with several glycolipid substrates showed high specificity of GM3-synthase for lactosylceramide. The apparent Km value for lactosylceramide and CMP-N-acetylneuraminic acid were 80 and 210 microM, respectively. The apparent molecular mass of the enzyme determined on SDS-polyacrylamide gel electrophoresis was 76 kDa.
J Biol Chem 1993 Dec 15
PMID:Purification and characterization of CMP-N-acetylneuraminic acid:lactosylceramide (alpha 2-3) sialyltransferase (GM3-synthase) from rat brain. 825 49

The beta-galactoside alpha-2,6-sialyltransferase is a trans Golgi/trans Golgi network glycosyltransferase which adds sialic acid residues to Asn-linked oligosaccharides of glycoproteins. Previous results suggested that the sialyltransferase stem and signal anchor including flanking sequences may be two independent Golgi retention regions. However, other experiments demonstrated that the sequence of the signal anchor itself was not important. To investigate whether the sialyltransferase signal anchor was necessary and sufficient for Golgi retention, several mutant and chimeric proteins were expressed and localized in Cos-1 and Chinese hamster ovary cells. We found that the signal anchor and flanking sequences were able to retain the sialyltransferase catalytic domain in the Golgi. However, efficient Golgi retention was still observed when the signal anchor was altered or entirely replaced in either the presence or absence of most of the luminal stem region. Chimeric proteins consisting of the sialyltransferase cytoplasmic tail and signal anchor fused to the extracellular domains of two different cell surface proteins demonstrated poor Golgi retention. A significant increase in the Golgi retention of one of these chimeras was observed when two lysines were placed next to the signal anchor on the luminal side. Taken together these results suggest that the sialyltransferase signal anchor is not necessary or sufficient for Golgi retention, rather, appropriately spaced cytoplasmic and luminal flanking sequences are the important elements of the sialyltransferase Golgi retention region.
J Biol Chem 1993 Dec 15
PMID:Specific sequences in the signal anchor of the beta-galactoside alpha-2,6-sialyltransferase are not essential for Golgi localization. Membrane flanking sequences may specify Golgi retention. 825 53

The activity of sialyltransferases with different linkage specificities, of a Gal beta 1-4GlcNAc:alpha 2,6-sialyltransferase and a Gal beta 1-4GlcNAc:alpha 2,3-sialyltransferase, was studied in human colorectal tumor tissue from surgical specimens, normal mucosa, liver and liver metastases, and serum of patients suffering from colorectal carcinomas. While alpha 2,3-specific activity was equally high in tumor and mucosa samples, the activity of the alpha 2,6-specific enzyme was increased in tumor tissue and particularly in metastasizing tumors. Also, compared to healthy individuals, serum of patients suffering from metastasizing tumors contained a significantly higher activity of the alpha 2,6-specific enzyme. These results demonstrate that specific sialyltransferase isoforms are expressed in metastasizing tumors and that determination of such isoforms may be a new means for tumor detection and monitoring.
Cancer Lett 1993 Dec 20
PMID:Enhanced activity of CMP-neuAc:Gal beta 1-4GlcNAc:alpha 2,6-sialyltransferase in metastasizing human colorectal tumor tissue and serum of tumor patients. 831 49

A human Gal beta(1-3/1-4)GlcNAc alpha 2,3-sialyltransferase, called ST-4, is a sialyltransferase involved in the in vivo biosynthesis of sialyl Lewis X (NeuNAc alpha 2-3Gal beta 1-4(Fuc alpha 1-3)GlcNAc) determinant. The ST-4 enzyme could utilize nLc4Cer (Gal beta 1-4GlcNAc beta 1-3Gal beta 1-4Glc beta 1-1'Cer) containing type 2 sugar chain, Lc4Cer (Gal beta 1-3GlcNAc beta 1-3Gal beta 1-4Glc beta 1-1'Cer) containing type 1 sugar chain, Gg4Cer (Gal beta 1-3GalNAc beta 1-3Gal beta 1-4Glc beta 1-1'Cer), and LacCer as glycolipid acceptor substrates, but not other neutral glycolipids (GalCer, GlcCer, Gb3Cer, Gg3Cer, Gb4Cer) and gangliosides (GM1a, GM2, GM3, GD1a, GD1b, and GT1b) as substrates. The order of sialic acid incorporation into glycolipids for the enzyme was nLc4Cer > Gg4Cer > Lc4Cer > LacCer. The apparent Km values of ST-4 for nLc4Cer and Gg4Cer were 0.47 and 2.5 mM, respectively. Thus, the ST-4 could efficiently utilize both nLc4Cer and Gg4Cer as glycolipid acceptor substrates in vitro, suggesting that the substrate specificity of the enzyme may be similar to that of a glycolipid sialyltransferase (SAT-3), which is defined as the enzyme that uses both nLc4Cer and Gg4Cer as glycolipid acceptor substrates.
Biochem Biophys Res Commun 1995 Dec 26
PMID:Glycolipid acceptor specificity of a human Gal beta(1-3/1-4) GlcNAc alpha 2,3-sialyltransferase. 855 8


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