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:2.4.99.7 (sialyltransferase)
1,534 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A sialyltransferase activity present in 7- to 12-day-old embryonic chicken brain catalyzes the transfer of sialic acid from CMP-sialic acid to the terminal galactose residue of [3H]nLcOse4Cer ([3H]Gal(beta 1-4).GlcNAc(beta 1-3)Gal(beta 1-4)Glc-Cer) to form NeuAc(alpha 2-3)-[3H]nLcOse4Cer (LM1 ganglioside). The product is sialidase-labile (96%), and the NeuAc group is linked to O-3 of the terminal galactose residue. The (alpha 2-3) linkage between sialic acid and the terminal galactose was determined on the basis of identification of 2,4,6-tri-O-methyl[3H]galactose obtained after hydrolysis of the permethylated enzymatic product. The CMP-sialic acid:nLcOse4Cer (alpha 2-3)sialyltransferase activity sediments (90%) at the junction of 1.2 M and 1.5 M on a discontinuous sucrose density gradient when still membrane bound (insoluble in 0.2% Triton X-100). The enzyme preparation also catalyzes the transfer of sialic acid from CMP-sialic acid to O-3 of GgOse4Cer (Gal(beta 1-3)GalNAc(beta 1-4)Gal(beta 1-4)Glc-Cer) to form NeuAc (alpha 2-3)GgOse4Cer (GM1b). Substrate inhibition studies indicate that these two reactions are probably catalyzed by the same enzyme.
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PMID:Biosynthesis in vitro of sialyl(alpha 2-3)neolactotetraosylceramide by a sialyltransferase from embryonic chicken brain. 713 Jan 78

A Gal beta 1 to 4GlcNAc alpha 2 to 6 sialyltransferse and a Gal beta 1 to 3(4)GlcNAc alpha 2 to 3 sialyltransferase have been purified 23,000- and 860,000-fold to homogeneity from Triton CF-54 extracts of rat liver membranes. The two enzymes were concentrated by affinity chromatography on CDP-hexanolamine-agarose and resolved by NaCl gradient elution from the same adsorbent. Final purification of the Gal beta 1 to 4GlcNAc alpha 2 to 6 sialytransferase, the most abundant enzyme, was achieved by specific elution from CDP-agarose with CDP. The Gal beta 1 to 3(4)GlcNAc alpha 2 to 3 sialyltransferase was also purified further by CDP elution from CDP-agarose, but final purification required affinity chromatography on an adsorbent prepared by coupling asialoprothrombin to cyanogen bromide-activated agarose. Asialoprothrombin contains the terminal sequence Gal beta 1 to 3GlcNAc on N-linked oligosaccharides and is the best acceptor substrate of the enzyme (Km congruent to 6 microM). The Gal beta 1 to 3(4)GlcNAc alpha 2 to 3 sialyltransferase was found to bind to asialoprothrombin-agarose in the presence of CDP and could be eluted with a solution containing 0.2 M lactose and no CDP. Sodium dodecyl sulfate-gel electrophoresis of the Gal beta 1 to 4GlcNAc alpha 2 to 6 and Gal beta 1 to 3(4)GlcNAc alpha 2 to 3 sialyltransferases revealed a single major protein band for each enzyme with apparent molecular weights of 40,500 and 44,000, respectively. Rabbit antibodies raised to the Gal beta 1 to 4GlcNAc alpha 2 to 6 sialyltransferase inhibit its enzymatic activity greater than 99% but caused little or no inhibition of Gal beta 1 to 3(4)GlcNAc alpha 2 to 3 sialytransferase. Moreover, the Gal beta 1 to 4GlcNAc alpha 2 to 6 sialyltransferase quantitatively bound to a column containing antibody adsorbed to Protein A-agarose, while the Gal beta 1 to 3(4) GlcNAc alpha 2 to 3 sialyltransferase did not bind. This demonstrated that the two sialyltransferases are antigenically unrelated and formed the basis for removal of contaminating Gal beta 1 to 4GlcNAc alpha 2 to 6 sialyltransferase from solutions of the Gal beta 1 to 3(4)GlcNAc alpha 2 to 3 sialyltransferase. Enzymatic characterization of the two sialyltransferases suggests that their major biological roles are in the terminal glycosylation of N-linked oligosaccharides of glycoproteins. (Weinstein, J., de Souza-e-Silva, U., and Paulson J. C. (1982) J. Biol. Chem. 257, 13845-13853. The alpha 2 to 6 sialyltransferase efficiently forms the NeuAc alpha 2 to 6Gal beta 1 to 4GlcNAc sequence, and the alpha 2 to 3 sialyltransferase forms the NeuAc alpha 2 to 3Gal beta 1 to 3GlcNAc and NeuAc alpha 2 to 3Ga; beta 1 to 4GlcNAc sequences.
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PMID:Purification of a Gal beta 1 to 4GlcNAc alpha 2 to 6 sialyltransferase and a Gal beta 1 to 3(4)GlcNAc alpha 2 to 3 sialyltransferase to homogeneity from rat liver. 714 79

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.
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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

The product of the MUC1 gene, the polymorphic epithelial mucin (PEM) is aberrantly glycosylated in breast and other carcinomas, resulting in exposure of normally cryptic peptide epitopes. PEM expressed by breast cancer cells contains more sialylated O-glycans and has a lower GlcNAc content than that expressed by normal cells. The exposure of peptide epitopes is thus thought to be due to the sugar side chains being shorter on the tumour-associated mucin. To investigate possible mechanisms underlying the different pattern of glycosylation in breast cancer cells, we analysed the pathways involved in the biosynthesis of O-glycan chains of mucins in normal and cancerous mammary epithelial cells. An immortalized mammary epithelial cells line originating from normal human milk. MTSV1-7, and three human breast cancer cell lines, BT20, MCF-7 and T47D, were studied. Glycosyltransferase activities assembling, elongating and terminating O-glycan core-1 [Gal beta 1-3GalNAc alpha-R] and core-2 [GlcNac beta 1-6 (Gal beta 1-3) GalNAc alpha-R] were present in the normal mammary cell line. Many of the glycosyltransferase activities were also expressed at variable levels in breast cancer cells. However, a sialyltransferase activity (CMP-sialic acid Gal beta 1-3GalNAc alpha 3-sialyltransferase) was increased several fold in all three cancer cell lines. Moreover, mammary cancer cell lines BT20 and T47D have lost the ability to synthesize core-2, as shown by the lack of UDP-GlcNAc: Gal beta 1-3GalNAc (GlcNAc to GalNAc) beta 6-GlcNAc-transferase activity, which corresponded to the absence of the mRNA transcript. However, MCF-7 breast cancer cells expressed this enzyme. Thus, the mechanism for the exposure of peptide epitopes in BT20 and T47D cells is proposed to be the loss of core-2 branching leading to shorter, sialylated O-glycan chains. A different mechanism is proposed for MCF-7 breast cancer cells.
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PMID:Mechanisms underlying aberrant glycosylation of MUC1 mucin in breast cancer cells. 758 8

Carbohydrate-deficient transferrin (CDT) is now considered to be the most sensitive and specific biological marker of alcohol abuse. However, the mechanism by which chronic alcohol consumption causes an elevation of CDT levels in serum is still not understood. Therefore, we fed eight pairs of male rats a nutritionally adequate liquid diet containing either alcohol (36% of energy) or isocaloric dextrose (control) for 4 weeks, after which blood and liver samples were obtained. Serum CDT content in alcohol-treated rats increased by 45% (P < .05) in ethanol-fed animals compared with their corresponding controls. In contrast, in rats fed ethanol, the activities of sialyltransferase (ST), galactosyltransferase (GT), and N-acetylglucosamine transferase (N-AGT), which are glycosyltransferases involved in transferrin carbohydrate side chain synthesis, were diminished by 24% and 40% (P < .05), 23% and 51% (P < .05, .001), and 20% and 26% (P < .05) in total liver homogenates and Golgi fraction (GF) 1, respectively, when expressed as units/100 g body weight. These enzymes were also significantly less active in hepatic GFs 2 and 3. The depression of the transferase activities in ethanol-fed rats appeared to be due, at least in part, to enzyme inactivation by acetaldehyde, whereas ethanol itself was without effect. Similar results were obtained in humans: five alcohol abusers were found to exhibit a 23% decrease in hepatic sialyltransferase and a 41% increase in sialidase activities, respectively, when compared with three nondrinking subjects.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Serum carbohydrate-deficient transferrin: mechanism of increase after chronic alcohol intake. 759 Jun 64

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.
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PMID:Identification of the gonococcal glmU gene encoding the enzyme N-acetylglucosamine 1-phosphate uridyltransferase involved in the synthesis of UDP-GlcNAc. 759 84

The sialyl-Lex determinant (NeuAc alpha 2-->3Gal beta 1-->4[Fuc alpha- 1-->3]GlcNAc) has been identified as a major ligand in the selectin-mediated adhesion of neutrophils and monocytes to activated endothelium or platelets. This carbohydrate epitope is formed by the sequential action of alpha 3-sialyltransferase and alpha 3-fucosyltransferase on N-acetyllactosamine (Gal beta 1-->4GlcNAc) disaccharide termini of glycoconjugates. We have addressed the role of the human myeloid alpha 3-fucosyltransferase in the expression of this epitope at the leucocyte surface by determining its activity in human-mouse leukemic cell hybrids (WEGLI), normal human granulocytes and chronic myeloid leukemia (CML) cells using sialylated and desialylated glycoproteins and oligosaccharides as acceptor substrates. In contrast to what has been reported for the myeloid-type enzyme, we found that the alpha 3-fucosyltransferase of the cells studied can use sialylated acceptors be it that the activity is several times lower than with asialo-substrates. Characterization of the product obtained with a sialylated oligosaccharide indicated that the enzyme can catalyze the formation of the sialyl-Le(x) structure. Flow cytometry of the WEGLI cells using a sialyl-Le(x)-specific monoclonal antibody (MoAb) showed that these cells indeed express sialyl-Lex at their surface, provided that they contain human chromosome 11. Earlier the presence of this chromosome had been correlated with the expression of alpha 3-fucosyltransferase activity. In addition to sialyl-Le(x), WEGLI cells containing chromosome 11 showed high-expression levels of related structures recognized by antibodies VIM-2 and VIM-8, suggesting that fucose addition can occur at both distal and proximal GlcNAc residues in poly-N-acetyl-lactosaminoglycan sequences. Based on the human chromosome contents it could be ruled out that the alpha 3-fucosyltransferase of WEGLI cells is a Lewis-type alpha 3/4- or plasma-type alpha 3-fucosyltransferase, the genes of which have been mapped to chromosome 19. It is concluded that the enzyme studied is of the myeloid-type and indeed is involved in the synthesis of sialyl-Le(x) (and also VIM-2 and VIM-8 structures) in leukocytes provided that its expression is at a sufficiently high level.
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PMID:Human myeloid alpha 3-fucosyltransferase is involved in the expression of the sialyl-Lewis(x) determinant, a ligand for E- and P-selectin. 768 23

1. Proteins that are released into the circulation in elevated amounts in injured mammals are referred to as acute-phase reactants. Most are liver synthesized glycoproteins of the secretable type. However, Gal-beta(1-->4)-GlcNAc-alpha(2-->6)-sialyltransferase (EC 2.4.99.1) is a novel acute-phase reactant since it is a Golgi membrane-bound enzyme rather than a secretable glycoprotein. 2. The role of glucocorticoids and cytokines in the control of synthesis and expression of acute-phase glycoproteins, including sialyltransferase, is discussed. 3. The acute-phase behaviour of Gal-beta(1-->4)-GlcNAc-alpha(2-->6)-sialyltransferase is dependent on the release of the enzyme from the Golgi in the acute-phase state. The mechanism of release of a catalytically active form of the enzyme is described.
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PMID:Sialyltransferase: a novel acute-phase reactant. 768 61

Sialyl-Lewisx (NeuAc alpha 2-->3Gal beta 1-->4[Fuc alpha 1-->3]GlcNAc] has been identified as a ligand for E-selectin, P-selectin and recently also for L-selectin. We have synthesized the sialyl-Lewisx tetrasaccharide by total enzymatic synthesis from N-acetyllactosamine using a placental alpha 2-->3-sialyltransferase specific for type-2 chain acceptors, followed by a cloned human alpha 1-->3-fucosyltransferase (FucTV, the 'plasma-type' enzyme). This procedure resulted in the tetrasaccharide in a 61% overall yield.
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PMID:Efficient enzymatic synthesis of the sialyl-Lewisx tetrasaccharide. A ligand for selectin-type adhesion molecules. 769 Jul 13

The activities of Gal beta 1-3(4)GlcNAc alpha 2-3 sialyltransferase and SAT-1 were measured in rat liver Golgi in inflammation; both enzymes decreased by about 50%. This compares with increases of about 3-fold for the Gal beta 1-4GlcNAc alpha 2-6 sialyltransferase. All three sialyltransferases were released from disrupted Golgi membranes by incubation at reduced pH which activates an endogenous cathepsin D which is believed to be the lysosomal enzyme. Pepstatin A was found to block the release of all three sialyltransferases providing support for the role of cathepsin D as the proteinase that clips the catalytic portions of the enzymes from their membrane anchor and stem regions.
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PMID:Release of sialyltransferases from rat liver Golgi membranes by a cathepsin D-like proteinase: comparison of the release of Gal beta 1-4GlcNAc alpha 2-6 sialyltransferase, Gal beta 1-3(4)GlcNAc alpha 2-3 sialyltransferase and lactosylceramide alpha 2-3 sialyltransferase (SAT-1). 771 47


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