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)

The distribution of beta 1,2 N-acetylglucosaminyltransferase I (NAGT I), alpha 1,3-1,6 mannosidase II (Mann II), beta 1,4 galactosyltransferase (GalT), alpha 2,6 sialyltransferase (SialylT) was determined by immuno-labelling of cryo-sections from HeLa cell lines. Antibody labelling in the HeLa cell line was made possible by stable expression of epitope-tagged forms of these proteins or forms from species to which specific antibodies were available. NAGT I and Mann II had the same distribution occupying the medial and trans cisternae of the stack. GalT and SialylT also had the same distribution but they occupied the trans cisterna and the trans-Golgi network (TGN). These results generalise our earlier observations on the overlapping distribution of Golgi enzymes and show that each of the trans compartments of the Golgi apparatus in HeLa cells contains unique mixtures of those Golgi enzymes involved in the construction of complex, N-linked oligosaccharides.
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PMID:Mapping the distribution of Golgi enzymes involved in the construction of complex oligosaccharides. 761 80

The glycocalyx, present on the surface of the corneal epithelium, contains sialoglycoconjugates. The developmental change in the sialylated residues may be evaluated by examining the expression of the sialyltransferase mRNA. We examined the distribution of Gal beta 1,3GalNAc alpha 2,3-sialyltransferase mRNA in rat corneas during development using in situ hybridization histochemistry to detect the starting point of the synthesis of O-linked sialoglycoconjugates. Eyelid opening occurred between postnatal days 14 (P14) and 16 (P16). In the corneal epithelium, little hybridization signal was observed until P12, whereas distinct hybridization signals were identified at P14 and thereafter. The expression of alpha 2,3-sialyltransferase mRNA is developmentally regulated, based on the programmed time-course of the gene expression, and the corneal epithelium may start to synthesize O-linked sialoglycoconjugates prior to the critical eyelid opening stage.
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PMID:Expression of distribution of alpha 2,3-sialyltransferase mRNA in rat cornea. 764 80

The synthesis of alpha 2,3-linked sialic acid to Gal(beta 1,3)GalNAc is mediated by at least three beta-galactoside alpha 2,3-sialyltransferases (EC 2.4.99.4, SiaT-4) that are encoded by three distinct genes. In contrast, only a single gene encodes the beta-galactoside alpha 2,6-sialyltransferase (EC 2.4.99.1, SiaT-1). This report assesses the relationship and nature of the SiaT-4 genes. Analysis of human-mouse somatic cell hybrids demonstrates that the sialyltransferase genes are dispersed in the human genome. The gene for SiaT-4 resides in chromosome 8, that for SiaT-4b resides in p21-p34 of chromosome 1 and that for SiaT-4c in q23.3-qter of chromosome 11. The gene symbols for these genes have been designated SIAT4A, SIAT4B and SIAT4C, respectively. To assess the structural organization of one of the SiaT-4 genes, a human SiaT-4a cDNA from submaxillary glands was isolated and characterized. Rapid amplification of cDNA 5' ends (5'-RACE) analysis indicates an unusually long 1 kb 5'-untranslated leader. The catalytic domain of the cloned sequence was expressed in transfected cells and was shown to be competent in mediating the specific synthesis of sialic acid alpha 2,3 to Gal(beta 1,3)GalNAc-R. Genomic sequences for SiaT-4a were also isolated and examined. The data demonstrate that coding information for SiaT-4a protein is dispersed into seven discrete exon segments in a manner reminiscent of the SiaT-1 gene. Furthermore, as in the SiaT-1 gene, intervening sequences interrupt both sialylmotif domains, regions that are conserved among all known sialyltransferases.
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PMID:Three genes that encode human beta-galactoside alpha 2,3-sialyltransferases. Structural analysis and chromosomal mapping studies. 765 69

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

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

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.
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PMID:Alterations of O-glycan biosynthesis in human colon cancer tissues. 773 50

The activity of bovine colostrum CMP-NeuAc:Gal beta 1-->4GlcNAc beta-R alpha 2-->6-sialyltransferase (alpha 6-NeuAcT) toward oligosaccharides that form part of complex-type, N-linked glycans appears significantly reduced when a bisecting GlcNAc residue or additional branches are present, or when core GlcNAc residues are absent. By contrast human placenta CMP-NeuAc:Gal beta 1-->4GlcNAc beta-R alpha 2-->3-sialyltransferase (alpha 3-NeuAcT) is much less sensitive to structural variations in these acceptors. Furthermore the alpha 3-NeuAcT shows a much higher activity than the alpha 6-NeuAcT with oligosaccharides that form part of linear and branched lactosaminoglycan extensions. These results indicate that, in tissues that express both enzymes, branching and lactosaminoglycan formation of N-linked glycans will cause a shift from termination with alpha 2-->6-linked sialic acid to termination with alpha 2-->3-linked sialic acid residues. These findings provide an enzymatic basis for the sialic acid linkage-type patterns found on the oligosaccharide chains of N-glycoproteins.
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PMID:Branching and elongation with lactosaminoglycan chains of N-linked oligosaccharides result in a shift toward termination with alpha 2-->3-linked rather than with alpha 2-->6-linked sialic acid residues. 773 17

A cDNA clone encoding chick Gal beta 1,3GalNAc alpha 2,3-sialyltransferase (ST3Gal I) was isolated from a chick embryo brain cDNA library. The cDNA sequence included an open reading frame coding for 342 amino acids, and the deduced amino acid sequence showed 64% identity with that of the mouse enzyme. Northern blot analysis of chick embryos revealed that the ST3Gal I gene was expressed in early embryonic stages. The identity of the enzyme was confirmed by construction of a recombinant sialyltransferase in which the N-terminal part including the cytoplasmic tail and signal anchor domain was replaced with an immunoglobulin signal peptide sequence. This enzyme expressed in COS-7 cells exhibited transferase activity similar to that of mouse ST3Gal I.
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PMID:Molecular cloning and expression of chick Gal beta 1,3GalNAc alpha 2,3-sialyltransferase. 776 61

All members of the sialyltransferase gene family cloned to date contain a conserved region, the "sialylmotif," consisting of 48-49 amino acids in the center of the coding sequence. To investigate the function of this motif, mutant constructs of the Gal beta 1,4GlcNAc alpha 2,6-sialyltransferase were designed by site-directed mutagenesis, replacing 11 individual conserved amino acids with alanine. Each of the mutants was expressed in COS-1 cells, and eight of these retained sialyltransferase activity, allowing comparison of their enzymatic properties with that of the wild type enzyme. Kinetic analysis showed that six of eight mutants had a 3-12-fold higher Km for the donor substrate CMP-NeuAc relative to the wild type enzyme, while the Km values for the acceptor substrate were within 0.5-1.2-fold of the wild type for all eight mutants evaluated. The Ki of the donor substrate analog CDP was also evaluated for the recombinant sialyltransferase with the Val to Ala mutation at residue 220, which produced a 6-fold increase in Km of CMP-NeuAc. A corresponding increase in Ki of 3.4-fold was observed for CDP, indicating a decreased affinity for the cytidine nucleotide. Taken together, these results suggest that the conserved sialylmotif in the sialyltransferase gene family participates in the binding of the common donor substrate, CMP-NeuAc.
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PMID:The sialyltransferase "sialylmotif" participates in binding the donor substrate CMP-NeuAc. 782 76


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