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

---

Query: EC:3.1.1.53 (sialidase)
2,694 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Human leucocytes contain a freeze-stable sialidase (neuraminidase; EC 3.2.1.18) activity in addition to the better-characterized lysosomal freeze-labile enzyme. In order to discriminate between the sialidase activities detected with the synthetic fluorimetric substrate 4-methylumbelliferyl-alpha-D-N-acetylneuraminic acid (MU-Neu5Ac), different tritiated sialoglycoconjugate substrates were prepared. Using this sensitive radioactive assay system, leucocyte sialidase activity towards glycoproteins was shown to be labile to repeated freeze-thawing, but a Triton-stimulated activity towards gangliosides was entirely freeze-stable. Assay conditions were optimized for this freeze-stable ganglioside sialidase activity. Subcellular fractionation of mononuclear leucocytes (MNLs) on Percoll-density gradients showed that this ganglioside sialidase activity was entirely associated with the plasma membrane. Study of the detergent requirements showed that MNLs also demonstrated ganglioside sialidase activity when sodium cholate was present in place of Triton. Cholate-stimulated ganglioside sialidase activity was found to be entirely freeze-stable and localized at the plasma membrane. Studies on whole homogenates of MNLs demonstrated that the Triton-stimulated and cholate-stimulated activities showed similar acidic pH optima at < or = 3.9 and were both strongly inhibited by 2-deoxy-2,3-didehydro-N-acetylneuraminic acid and Cu2+, but not by free N-acetylneuraminic acid, N-(4-nitrophenyl)oxamic acid or heparan sulphate. These results suggest that human MNLs contain, in addition to the lysosomal freeze-labile sialidase, a single sialidase activity which is freeze-stable, ganglioside-specific, plasma membrane-associated and stimulated both by Triton and by cholate.
...
PMID:Freeze-stable sialidase activity in human leucocytes: substrate specificity, inhibitor susceptibility, detergent requirements and subcellular localization. 805 2

The release of 3-deoxy-D-glycero-D-galacto-2-nonulosonic acid (KDN, deaminoneuraminic acid) residues from their alpha-ketosidic linkage is required to determine the structural and functional role of KDN-glycoconjugates in sources as disparate as trout egg polysialoglycoproteins and human cancers. We report for the first time the isolation and characterization of a novel type of sialidase (KDNase), which specifically hydrolyzes KDN ketosidic but not N-acylneuraminyl linkages. KDNase activity was assayed using 4-methylumbelliferyl KDN (4-MU-KDN). A KDNase-producing microorganism was identified as Sphingobacterium multivorum. The affinity-purified enzyme was designated KDNase SM to denote its origin and that it was free of N-acylneuraminidase, proteolytic, and other glycosidase activities. KDNase SM activity toward 4-MU-KDN was not inhibited by the N-acylneuraminidase inhibitor, 2,3-dehydro-2-deoxy-N-acetylneuraminic acid. KDNase SM released free KDN from naturally occurring substrates, including (KDN)GM3, KDN-glycoprotein, which bears a number of O-linked chains of KDN alpha 2-->3Gal beta 1-->3GalNAc alpha 1-->3 (KDN alpha 2-->(-->8KDN alpha 2-->)n-->6)GalNAc alpha 1-->, and the biantennary complex-type of N-glycan, KDN alpha 2-->3Gal beta 1-->4GlcNAc beta 1-->2Man alpha 1-->6(KDN alpha 2-->3Gal beta 1-->4GlcNAc beta 1-->2Man alpha 1-->3)Man beta 1-->4GlcNAc beta 1-->4GlcNAc. KDNase SM thus exhibited a broad linkage specificity and was able to hydrolyze the KDN residues ketosidically linked alpha 2-->3, alpha 2-->6, and alpha 2-->8. The enzyme did not release Neu5Ac or Neu5Gc from 4-MU-Neu5Ac, N-acetyl-neuraminyllactose, colominic acid, or other Sia(Neu5Ac or Neu5Gc)-containing glycoconjugates.
...
PMID:Discovery of a new type of sialidase, "KDNase," which specifically hydrolyzes deaminoneuraminyl (3-deoxy-D-glycero-D-galacto-2-nonulosonic acid) but not N-acylneuraminyl linkages. 806 73

Water-soluble polyacrylamide having 3'-sialyl N-acetyl-lactosamine [Neu5Ac alpha (2-->3)Gal beta (1-->4)GlcNAc] was enzymatically prepared by stepwise sugar-elongation on a water-soluble GlcNAc-bearing polyacrylamide. It was demonstrated that the flexible GlcNAc branches of the polymer chains allow quantitative galactosylation with bovine galactosyl transferase and partial sialylation by Trypanosoma cruzi trans-sialidase. Unsialylated N-acetyl-lactosamine side chains can be removed with beta-D-galactosidase and N-acetyl-beta-D-glucosaminidase to afford the targeted polymer containing 3'-sialyl N-acetyl-lactosamine.
...
PMID:Chemoenzymic preparation of a glycoconjugate polymer having a sialyloligosaccharide: Neu5Ac alpha (2-->3)Gal beta (1-->4)GlcNAc. 812 20

A molecular modeling study has been used to investigate the structural and energetic aspects of substrate and inhibitor binding and the mechanism of catalysis of influenza virus sialidase. A detailed analysis of the interactions of both N-acetylneuraminic acid (Neu5Ac,1) and a number of transition-state analogues with the active site of influenza A sialidase at an atomic level is reported. In each case the calculated structures favorably agreed with the results from X-ray studies. A qualitative agreement between the calculated binding energies for inhibitors with positive substituents at the C4 position on the sugar ring and experimental Ki values was observed. We propose that the hydrolysis of sialosides occurs via an SN1 type mechanism that is facilitated through an activated solvent water molecule which can be expelled upon inhibitor binding. A reaction scheme is presented that is consistent with previously observed crystallographic structures, anomeric products, and isotope effects.
...
PMID:Molecular modeling studies on ligand binding to sialidase from influenza virus and the mechanism of catalysis. 812 1

In a previous report (Kitajima, K., Inoue, S., and Inoue, Y. (1989) Dev. Biol. 132, 544-553), we found the presence of a heavily glycosylated polyprotein, "H-hyosophorin," isolated from the unfertilized eggs of Oryzias latipes. We now report our detailed analysis of the structure of the N-glycan chain in L-hyosophorin, the smallest repeating unit of H-hyosophorin, which was isolated from the fertilized eggs of O. latipes and formed from H-hyosophorin upon fertilization. The N-glycan structures were defined by a combination of compositional analysis, methylation analysis, selective chemical degradation (i.e. mild methanolysis, periodate-Smith degradation, and hydrazinolysis-nitrous acid deamination), enzymatic (endo-beta-galactosidase, peptide:N-glycanase, and Newcastle disease virus sialidase) digestion, and instrumental analyses (one- and two-dimensional proton nuclear magnetic resonance spectroscopy and fast atom bombardment mass spectrometry) which revealed novel and unique features: (a) the presence of highly branched poly-N-acetylactosamino pentaantennary structures; (b) the presence of a beta-galactosylated Lewis X antigenic epitope, Gal beta 1-->4 Gal beta 1-->4 (Fuc alpha 1-->3) GlcNAc beta 1-->; (c) the presence of a beta-galactosylated sialyl Lewis X structure, Gal beta 1-->4 (Neu5Ac alpha 2-->3) Gal beta 1-->4(Fuc alpha 1-->3) GlcNAc beta 1-->; (d) the presence of Gal beta 1-->4 Gal beta 1--> and Gal beta 1--> 4Gal beta 1-->4Gal beta 1--> as the major and minor groupings, respectively; and (e) the presence of the branched Gal residues, -->4GlcNAc beta 1-->3(Gal beta 1-->4) Gal beta 1-->. This study represents the first detailed investigation regarding the nature of highly branched complex asparagine-linked pentaantennary glycans in glycoproteins. The unique expression of such bulky multiantennary glycan units on proteins could be essential during early embryogenesis.
...
PMID:Structural studies of a novel type of pentaantennary large glycan unit in the fertilization-associated carbohydrate-rich glycopeptide isolated from the fertilized eggs of Oryzias latipes. 813 8

We have examined the tissues of several species of fish and found that the liver of the loach (Misgurnus fossilis) contains a novel sialidase capable of efficiently hydrolyzing 3-deoxy-D-glycero-D-galacto-2-nonulosonic acid (KDN) from the 4-methylumbelliferyl alpha-ketoside of KDN, KDN alpha 2-->3Gal beta 1-->4GlcCer and KDN alpha 2-->6 N-acetylgalactosaminitol as well as Neu5Ac from the 4-methylumbelliferyl alpha-ketoside of Neu5Ac and GM3. The pH optimum for this enzyme was determined to be 4.6, and the Km using the 4-methylumbelliferyl alpha-ketoside of KDN and 4-methylumbelliferyl alpha-ketoside of Neu5Ac as substrates were 0.07 and 0.12 mM, respectively. The enzyme was stable in the pH range of 4 to 5 but very unstable above pH 6. This is the first report of a sialidase capable of efficiently cleaving glycosidically linked KDN.
...
PMID:A novel sialidase capable of cleaving 3-deoxy-D-glycero-D-galacto-2-nonulosonic acid (KDN). 816 Dec 11

Donor specificity of Trypanosoma cruzi trans-sialidase (TcTs) has been investigated with modified 2-[4-methylumbelliferone]-alpha- ketoside of N-acetyl-D-neuraminic acid (4MU-NANA) as donor and lactose as acceptor. 4MU-NANA was treated with periodate under mild conditions to generate an aldehyde on the exocyclic side chain. The oxidized 4MU-NANA was derivatized with various primary amines by reductive amination to yield potential donors. High-performance anion-exchange chromatography equipped with pulsed amperometric detector was used to assay the transglycosylation activity of TcTs. Several modified 4MU-NANA derivatives served as substrates by TcTs and they may be utilized to make valuable intermediates, including those for fluorescence energy transfer measurement or photoaffinity labeling experiment.
...
PMID:Transfer of modified sialic acids by Trypanosoma cruzi trans-sialidase for attachment of functional groups to oligosaccharide. 817 90

Trypanosomes cannot synthesize sialic acids. Infectious stages of the life cycle of the human pathogen Trypanosoma cruzi express a cell-surface glycolipid-anchored trans-sialidase, which can transfer sialic acid between glyco-conjugates. Sialic acid is transferred from host cell-surface and serum sialylglycoproteins to trypanosome cell-surface glycoconjugates. The transfer reaction is specific for donors with terminal alpha-2,3-linked sialic acid, and terminal beta-1,4-linked galactose is the preferred acceptor. In the absence of an acceptor, the enzyme acts as a hydrolase, but cleavage is less efficient than transfer. Trans-sialidase activity is attributable to a few members of a large family of T. cruzi surface glycoproteins, many of which are simultaneously expressed. The functions of the trans-sialidase surface glycoprotein family are unknown but may be important for adhesion, invasion, virulence, or pathogenicity. A trans-sialidase is also expressed in the procyclic forms of Trypanosoma brucei.
...
PMID:The surface trans-sialidase family of Trypanosoma cruzi. 825 3

A developmentally regulated trans-sialidase activity is present on the surface of procyclic Trypanosoma brucei. Bloodstream stages display no trans-sialidase activity. T. brucei trans-sialidase is capable of transferring sialic acids from a variety of glycoconjugates into new glycosidic linkages without requirement for CMP-Neu5Ac. The enzyme is linked to the plasma-membrane via a GPI-PLC-resistant GPI-anchor. The comparison of enzymic and structural features of sialidase and trans-sialidase suggests that the two activities may be catalyzed by the same protein, since highly enriched sialidase fractions display trans-sialidase activity. 2-Deoxy-2,3-didehydro-N-acetylneuraminic acid is only a poor inhibitor for the two enzymic activities. Sialic acids are transferred to alpha (2-3)-positions of terminal beta-galactose residues of oligosaccharides and glycoconjugates at various rates. Neu5Ac-alpha(2-3)-lactose is the best trans-sialylation donor tested. Lewis is a poor sialic acid acceptor. T. brucei trans-sialidase utilizes serum glycoconjugates, human and bovine erythrocytes as sialic acid donors, and resialylates sialidase-treated erythrocytes. The enzyme transfers sialic acids from the GPI-anchor of procyclic acidic repetitive protein (PARP) onto lactose and vice versa. Also structures within a variant surface glycoprotein (sVSG MITat. 1.7.) can be trans-sialylated.
...
PMID:The developmentally regulated trans-sialidase from Trypanosoma brucei sialylates the procyclic acidic repetitive protein. 825 22

When a rat liver Golgi apparatus-enriched subcellular fraction is incubated with UDP-[3H]Gal, CMP-[3H] Neu5Ac, or [acetyl-3H]acetyl (Ac)-CoA, label is efficiently transferred to endogenous acceptors, which are resistant to added proteases, unless detergent is added at a sufficiently high concentration. Thus, the acceptors are within the lumen of intact compartments of correct topological orientation, which are likely to be similar to those of the Golgi apparatus in the intact cell. In each case, approximately 90% of the macromolecular radioactivity is specifically released by peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine amidase digestion, as labeled N-linked oligosaccharides. Label from UDP-[3H]Gal is transferred to several distinct N-linked oligosaccharides, and many of these carry sialic acid (Sia) residues. This amount increases if the transfer reaction is chased with CMP-Neu5Ac. A major fraction of the [3H]Gal is directly "covered" with Sia residues, indicating that at least a portion of the beta-galactosyltransferase(s) are co-localized with one or more sialyltransferases. The majority of the [3H]Gal is found in a beta 1,3-linkage, rather than the more common beta 1,4-linkage. The N-linked oligosaccharides labeled by CMP-[3H] Neu5Ac carry labeled Sia residues in either alpha 2,3 or alpha 2,6 linkage, and showed a range of charge distribution. The transferred [3H]Neu5Ac is not O-acetylated even when Ac-CoA is added at saturating concentrations, implying that the sialyltransferases and the O-acetyltransferase(s) are not functionally co-localized. However, approximately 20% of label released from N-linked oligosaccharides by sialidase does not co-migrate with authentic Neu5Ac in high performance liquid chromatography analysis, indicating that transferred [3H] Neu5Ac is modified by unknown enzymes in the Golgi. Most of the [3H]acetate transferred from [acetyl-3H] Ac-CoA to N-linked oligosaccharides is on Sia residues that are exclusively alpha 2,6-linked, and is enriched on tri- and tetra-antennary chains that do not appear to carry any 2,3-linked Sia residues. These data indicate a restricted substrate preference of the O-acetyltransferase(s). About one-quarter of the [3H]acetate transferred is sialidase-resistant, indicating either transfer to monosaccharides other than sialic acid, or to sialidase-resistant sialic acids. While most of these sialidase-resistant oligosaccharides remain negatively charged, about 10% are neutralized by sialidase, confirming transfer of [3H]acetate to monosaccharides other than sialic acid.
...
PMID:Biosynthesis of oligosaccharides in intact Golgi preparations from rat liver. Analysis of N-linked glycans labeled by UDP-[6-3H]galactose, CMP-[9-3H]N-acetylneuraminic acid, and [acetyl-3H]acetyl-coenzyme A. 834


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>

---