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)

Poly-alpha-2,8 N-acetylneuraminic acid (polySia) is an important virulence factor in infections caused by Escherichia coli K1 and Neisseria meningitidis B. In E. coli K1 a membranous CMP-NeuAc: poly-alpha-2,8 sialosyl sialyltransferase (polysialyltransferase) complex catalyses the synthesis of linear polySia chains. The complex also elongates sialyl oligomers that serve as exogenous acceptors. The gene encoding a polysialyltransferase of E. coli has been identified by subcloning and DNA sequence analysis. The subcloned DNA fragment codes for a polypeptide with a molecular mass of 47 kDa catalysing the in vitro synthesis of polySia by elongation of exogenous acceptors.
Glycobiology 1991 Sep
PMID:Complete nucleotide and deduced protein sequence of CMP-NeuAc: poly-alpha-2,8 sialosyl sialyltransferase of Escherichia coli K1. 182 Jan 97

The glycosyltransferases controlling the biosynthesis of cell-surface complex carbohydrates transfer glycosyl residues from sugar nucleotides to specific hydroxyl groups of acceptor oligosaccharides. These enzymes represent prime targets for the design of glycosylation inhibitors with the potential to specifically alter the structures of cell-surface glycoconjugates. With the aim of producing such inhibitors, synthetic oligosaccharide substrates were prepared for eight different glycosyltransferases. The enzymes investigated were: A, alpha(1----2, porcine submaxillary gland); B, alpha(1----3/4, Lewis); C, alpha(1----4, mung bean); D, alpha(1----3, Lex)-fucosyltransferases; E, beta(1----4)-galactosyltransferase; F, beta(1----6)-N-acetylglucosaminyltransferase V; G, beta(1----6)-mucin-N-acetylglucosaminyltransferase ("core-2" transferase); and H, alpha(2----3)-sialyltransferase from rat liver. These enzymes all transfer sugar residues from their respective sugar nucleotides (GDP-Fuc, UDP-Gal, UDP-GlcNAc, and CMP-sialic acid) with inversion of configuration at their anomeric centers. The Km values for their synthetic oligosaccharide acceptors were in the range of 0.036-1.3 mM. For each of these eight enzymes, acceptor analogs were next prepared where the hydroxyl group undergoing glycosylation was chemically removed and replaced by hydrogen. The resulting deoxygenated acceptor analogs can no longer be substrates for the corresponding glycosyltransferases and, if still bound by the enzymes, should act as competitive inhibitors. In only four of the eight cases examined (enzymes A, C, F, and G) did the deoxygenated acceptor analogs inhibit their target enzymes, and their Ki values (all competitive) remained in the general range of the corresponding acceptor Km values. No inhibition was observed for the remaining four enzymes even at high concentrations of deoxygenated acceptor analog. For these latter enzymes it is suggested that the reactive acceptor hydroxyl groups are involved in a critical hydrogen bond donor interaction with a basic group on the enzyme which removes the developing proton during the glycosyl transfer reaction. Such groups are proposed to represent logical targets for irreversible covalent inactivation of this class of enzyme.
J Biol Chem 1991 Sep 25
PMID:Evaluation of deoxygenated oligosaccharide acceptor analogs as specific inhibitors of glycosyltransferases. 191 26

The rat beta-galactoside alpha 2,6-sialytransferase gene is differentially utilized by liver and kidney in the generation of mRNAs that predict substantially divergent polypeptides. In order to determine the biosynthetic relationship between these sialyltransferase mRNA isoforms, genomic sequences were isolated and analysed. Five exons that span at least 40 kb of DNA carry the coding information for the liver beta-galactoside alpha 2,6-sialyltransferase protein. An additional exon contains only sequences for the 5'-untranslated leader of the liver mRNA. In contrast, the predominant kidney mRNAs from this gene share only three coding exons that specify the carboxyl terminal 42% of the liver sialyltransferase protein sequence. In addition, these kidney mRNAs contain information from two other exons that comprise the 5' divergent region of these transcripts. Primer extension and S1 nuclease protection analysis demonstrate that the hepatic and kidney specific mRNAs are transcriptionally initiated at different sites within the sialyltransferase gene. While the hepatic sialyltransferase mRNAs are transcribed from the first exon, the kidney transcripts are initiated from a site within the third intron. Genomic regions upstream of both transcriptional initiation sites can regulate expression of the bacterial chloramphenicol acetyltransferase gene in transiently transfected L cells. Together, the data implicate multiple promoters as a principle mechanism in the generation of kidney and liver gene product diversity in sialyltransferase expression.
Glycobiology 1990 Sep
PMID:Rat beta-galactoside alpha 2,6-sialyltransferase genomic organization: alternate promoters direct the synthesis of liver and kidney transcripts. 198 83

beta 1,4-N-Acetylgalactosaminyltransferase (beta 1,4GalNAc-transferase) and alpha 2,3-sialyltransferase are both involved in the biosynthesis of the Sda blood group antigen, which is also present in cells of large intestine. The expression of these enzymes and of alpha 2,6-sialyltransferase activity towards N-acetyl-lactosamine was investigated in rat intestinal cells and correlated with both cell differentiation and extent of postnatal maturation. The beta 1,4GalNAc-transferase activity was exclusively found in epithelial cells of the large intestine, preferentially in the proximal segments suggesting a proximal-distal gradient of expression. The beta 1,4GalNAc-transferase and alpha 2,3-sialyltransferase activity towards N-acetyl-lactosamine were expressed in all cell fractions of the colonic crypt, with a maximum activity in the deeply located cells; therefore Sda antigen biosynthesis appears to occur preferentially at a specific stage of cell differentiation. By using N-acetyl-lactosamine as an acceptor, the predominant sialyltransferase in the colon cells was that capable of adding sialic acid in the alpha 2,3- linkage, whereas in the ileum cells the major enzyme was that forming the alpha 2,6-isomer. There were dramatic changes in the expression of colonic beta 1,4GalNac-transferase and of alpha 2,6-sialyltransferase activity towards N-acetyl-lactosamine during postnatal maturation. The former enzyme, practically absent at birth, increased slowly in the first days of life and then rapidly after weaning; by contrast, the latter enzyme was largely expressed only in newborn animals. As the colonic alpha 2,3-sialyltransferase activity towards N-acetyl-lactosamine did not change during the postnatal period, the ratio between the alpha 2,6- and alpha 2,3-sialyltransferase activities was reversed after weaning.
Biochem J 1990 Sep 01
PMID:Postnatal development of rat colon epithelial cells is associated with changes in the expression of the beta 1,4-N-acetylgalactosaminyltransferase involved in the synthesis of Sda antigen of alpha 2,6-sialyltransferase activity towards N-acetyl-lactosamine. 211 76

The Golgi complex is composed of at least four distinct compartments, termed the cis-, medial, and trans-Golgi cisternae and the trans-Golgi network (TGN). It has recently been reported that the organization of the Golgi complex is disrupted in cells treated with the fungal metabolite, brefeldin-A. Under these conditions, it was shown that resident enzymes of the cis-, medial, and trans-Golgi return to the ER. We report here that 300-kD mannose 6-phosphate receptors, when pulse-labeled within the ER of brefeldin-A-treated cells, acquired numerous N-linked galactose residues with a half time of approximately 2 h, as measured by their ability to bind to RCA-I lectin affinity columns. In contrast, Limax flavus lectin chromatography revealed that less than 10% of these receptors acquired sialic acid after 8 h in brefeldin-A. Two lines of evidence suggested that proteins within and beyond the TGN did not return to the ER in the presence of brefeldin-A. First, the majority of 300-kD mannose 6-phosphate receptors present in the TGN and endosomes did not return to the ER after up to 6 h in brefeldin-A, as determined by their failure to contact galactosyltransferase that had relocated there. Moreover, although mannose 6-phosphate receptors did not acquire sialic acid when present in the ER of brefeldin-A-treated cells, they were readily sialylated when labeled at the cell surface and transported to the TGN. These experiments indicate that galactosyltransferase, a trans-Golgi enzyme, returns to the endoplasmic reticulum in the presence of brefeldin-A, while the bulk of sialyltransferase, a resident of the TGN, does not. Our findings support the proposal that the TGN is a distinct, fourth compartment of the Golgi apparatus that is insensitive to brefeldin-A.
J Cell Biol 1990 Sep
PMID:Compartmentation of the Golgi complex: brefeldin-A distinguishes trans-Golgi cisternae from the trans-Golgi network. 216 98

We have shown previously that low density lipoproteins (LDL) suppressed the synthesis of lactosylceramide in normal human proximal tubular cells, but stimulated such synthesis in proximal tubular cells from LDL receptor negative subjects (Chatterjee, S., Clarke, K., and Kwiterovich, P.O., Jr. (1986) J. Biol. Chem. 261, 13474-13479). To understand the mechanism(s) of this effect of LDL, we have studied here the effects of LDL on the activity of UDP-GalCer:beta-galactosyltransferase (GalT-2). Maximum suppression (70-80%) of the activity of GalT-2 in normal proximal tubular cells at 37 degrees C occurred at a LDL concentration of 25 micrograms/ml medium. Such suppression was not observed either when the cells were incubated with LDL at 4 degrees C, or when the cells were preincubated with leupeptin, followed by incubation with LDL at 37 degrees C. High density lipoproteins and fetuin did not suppress the activity of GalT-2 in normal proximal tubular cells. In contrast LDL modified by reductive methylation (M-LDL, 100 micrograms/ml) stimulated the activity of GalT-2, approximately 3-fold. The effects of LDL and M-LDL were not related to their glycosphingolipid content. Much less suppression and stimulation of the activity of GalT-2 in proximal tubular cells by LDL and M-LDL, respectively, was found in normal human skin fibroblasts, Chinese hamster ovary cells, and bovine smooth muscle cells, suggesting that the LDL-mediated effect may be tissue-specific. In cells grown to very high density, the activity of the LDL receptor is decreased, and there was less suppression of GalT-2 activity by LDL. In normal proximal tubular cells, LDL stimulated the activity of UDP-Gal:LacCer, alpha-galactosyltransferase activity, UDP-Gal:LcOse3Cer, beta-galactosyltransferase, and CMP-NeuAc:LacCer,alpha-sialyltransferase activity but did not alter the activity of sulfotransferase. In conclusion, LDL that entered the normal proximal tubular cells via the LDL receptor-mediated pathway decreased GalT-2 activity, an effect that was dependent upon the binding, internalization, and degradation of receptor-bound LDL. In contrast LDL that entered normal or LDL receptor-negative proximal tubular cells via an LDL receptor-independent pathway failed to suppress GalT-2 activity, and led to a stimulation of LacCer synthesis.
J Biol Chem 1988 Sep 15
PMID:Regulation of glycosphingolipid glycosyltransferase by low density lipoprotein receptors in cultured human proximal tubular cells. 245 39

The presence in the 100,000 g supernatant of rat brain homogenate of an inhibitor of the sialyltransferase has been confirmed. It is also present in chicken and bovine brain and in other rat and bovine organs. The inhibitor has been purified, a preparation with a specific activity 130-fold higher than that of the original 100,000 g supernatant of brain being obtained. It runs as a single peak in polyacrylamide-gel electrophoresis; when run in the presence of SDS, two components appeared. The apparent Mr of the components were 14,800 and 22,400. The inhibitor has been characterized as a heat-stable protein of acidic nature. It has effect on the glycolipid and the glycoprotein sialyltransferase activities but has no effect on the galactosaminyltransferase activity.
Biochem J 1988 Sep 01
PMID:Purification and characterization of an endogenous inhibitor of the sialyltransferase CMP-N-acetylneuraminate: lactosylceramide alpha 2,6-N-acetylneuraminyltransferase (EC 2.4.99.-). 246 92

The sialyltransferase activities of 10 human colorectal specimens were compared with those of the corresponding adjacent normal mucosa. Using asialofetuin as an acceptor we found, in tumor tissues of 9 out of 10 patients, an increased sialyltransferase activity towards the N-linked chains as determined upon peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine amidase (PNGase) treatment. On the contrary, the activity towards the O-linked chains was not significantly changed. When the specificity of the sialyltransferase acting on N-linked chains was investigated by using N-acetyl-lactosamine (Gal beta 1,4GlcNAc) as an acceptor, we found that the alpha 2,6 sialyltransferase activity expressed by both normal and tumor colorectal tissues was far higher than the alpha 2,3-activity and that alpha 2,6 was the only sialyltransferase activity increased in tumor tissues. Kinetic analysis revealed that normal and tumor alpha 2,6 sialyltransferases have the same apparent Km for the acceptor substrate (469 and 465 microns), but normal enzyme has a higher Km for CMP-NeuAc (303 microns) than the tumor enzyme (50 microns). The higher affinity of tumor enzyme for the nucleotide-sugar might partially explain its increased activity in tumor tissues. In addition, tumor tissues contain a lower amount of sialic acid despite the increase in alpha 2,6 sialyltransferase activity.
Int J Cancer 1989 Sep 15
PMID:Increased CMP-NeuAc:Gal beta 1,4GlcNAc-R alpha 2,6 sialyltransferase activity in human colorectal cancer tissues. 247 2

This paper presents kinetic properties of the transfer of several synthetic 9-substituted sialic acid analogues onto N- or O-linked glycoprotein glycans by four purified mammalian sialyltransferases: Gal beta 1,4GlcNac alpha 2,6sialyltransferase, Gal beta-1,4(3)GlcNAc alpha 2,3-sialyltransferase, Gal beta 1,3GalNAc alpha 2,3sialyltransferase, and GalNAc alpha 2,6sialyltransferase. The substituents at C-9 of the sialic acid analogues introduce special biochemical characteristics: 9-Amino-NeuAc represents, up to the present, the first derivative that is resistant toward bacterial, viral, and mammalian sialidases but is transferred by a sialyltransferase. 9-Acetamido-NeuAc, 9-benzamido-NeuAc, and 9-hexanoylamido-NeuAc differ in size and hydrophobic character from each other and from parent NeuAc. 9-Azido-NeuAc may be used to introduce a photoreactive label. The kinetic properties of the four sialyltransferases with regard to the donor CMP-glycosides differed distinctly depending on the structure of the substituent at C-9. CMP-9-amino-NeuAc was only accepted as donor substrate by Gal beta 1,4GlcNAc alpha 2,6sialyltransferase (rat liver), but the Km value was 14-fold higher than that of parent CMP-NeuAc. In contrast, 9-azido-NeuAc was readily transferred by each of these four enzymes. 9-Acetamido-NeuAc, which is a receptor analogue for influenza C virus, 9-benzamido-NeuAc, and 9-hexanoylamido-NeuAc were also accepted by each sialyltransferase, but incorporation values differed significantly depending on the enzyme used. For the first time, the resialylation of asialo-alpha 1-acid glycoprotein with 9-substituted sialic acid analogues by Gal beta 1,4GlcNAc alpha 2,6sialyltransferase is demonstrated.
Biochemistry 1989 Sep 05
PMID:Transfer of synthetic sialic acid analogues to N- and O-linked glycoprotein glycans using four different mammalian sialyltransferases. 251 Aug 24

A marked elevation of sialyltransferase activity (STA) was observed in a solid tumor of plasma cells, which had been removed from a patient with multiple myeloma (MM), as compared to normal lymphatic tissues. STA was also determined in mononuclear bone marrow cells of 10 patients with MM and found to be 12 times higher than that of bone marrow mononuclear cells from 5 patients with non-malignant disorders (with less than 1% plasma cells in the bone marrow aspirate). A significant correlation was found between STA and the number of plasma cells in the bone marrow aspirate.
Eur J Haematol 1989 Sep
PMID:Sialyltransferase activity in plasma cells of multiple myeloma. 280 73


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