Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.1.53 (sialidase)
 2,694 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Influenza C virus (strain C/Johannesburg/1/66) was grown, harvested, purified and used as source for the enzyme O-acetylesterase (N-acyl-O-acetylneuraminate O-acetylhydrolase; EC 3.1.1.53). This activity was studied and characterized with regard to some new substrates. The pH optimum of the enzyme is around 7.6, its stability at different pH values shows a result similar to that of the pH optimum, and its activity is well maintained in the pH range from 7.0 to 8.5 (all these tests were performed with 4-nitrophenyl acetate as substrate). Remarkable differences were found in the values of both Km and Vmax, with the synthetic substrates 4-nitrophenyl acetate, 2-nitrophenyl acetate, 4-methylumbelliferyl acetate, 1-naphthyl acetate and fluorescein diacetate. The use of 4-nitrophenyl acetate, 4-methylumbelliferyl acetate or 1-naphthyl acetate as substrate seems to be convenient for routine work, but it is better to carry out the measurements in parallel with those on bovine submandibular gland mucin (the latter is a natural and commercially available substrate). It was found that 4-acetoxybenzoic acid, as well as the methyl ester of 2-acetoxybenzoic acid, but not 2-acetoxybenzoic acid itself, are cleaved by this enzyme. Triacetin, di-O-acetyladenosine, tri-O-acetyladenosine, and di-O-acetyl-N-acetyladenosine phosphate, hitherto unreported as substrates for this viral esterase, are hydrolysed at different rates by this enzyme. We conclude that the O-acetylesterase from influenza C virus has a broad specificity towards both synthetic and natural non-sialic acid-containing substrates. Zn2+, Mn2+ and Pb2+ (as their chloride salts), N-acetylneuraminic acid, 4-methyl-umbelliferone and 2-acetoxybenzoic acid (acetylsalicylic acid) did not act as inhibitors.
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PMID:Activity of influenza C virus O-acetylesterase with O-acetyl-containing compounds. 199 Oct 39

Ca2+ increases the initial rate of activity of sialidase from influenza virus (A/Tokyo/3/67). Increasing ionic strength also activates influenza virus sialidase. When ionic strength is controlled, smaller but still significant Ca2+ effects are observed, with Vmax/Km increased from 0.8.10(5) to 1.4.10(5) M-1 s-1 and Vmax increased from 6.3 to 9.5 s-1 by saturating Ca2+. The Ki of the competitive inhibitor 2,3-dehydro-2-deoxy-N-acetylneuraminic acid was decreased from 2.7.10(-6) to 1.15.10(-6) M after the addition of saturating Ca2+. The data show that Ca2+ exerts a specific effect on Vmax/Km, leading to an increased rate of interaction of substrate with the enzyme. The Kd-app for the Ca2(+)-sialidase complex is 2 mM. Except for Mg2+ which behaves similarly to Ca2+, other mono- and divalent cations have little specific effect on sialidase kinetics. Sequence analysis of a range of subtypes of sialidases from influenza virus supports the proposal that Ca2+ binds at the subunit interface transmitting a conformational change to the enzyme active site. Ca2+ activation may have a physiological role in switching on sialidase activity during the release of newly synthesised virions from the host cell surface.
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PMID:Influenza virus sialidase: effect of calcium on steady-state kinetic parameters. 200 95

Rimantadine-resistant and -sensitive influenza A variants were assayed for their sialidase (neuraminidase, EC 3.2.1.18) activity. The kinetic parameters determined (pH optimum, stability against different pH values, thermal stability, activity on methylumbelliferyl-alpha-D-N-acetylneuraminic acid, N-acetylneuraminyl-lactose, fetuin and bovine submandibular gland mucin as substrates, Km with the former substrate, inhibition by two competitive inhibitors, and behavior towards amantadine) revealed the same results for both variants of the virus. Thus, it can be deduced that resistance to rimantadine does not influence the sialidase activity of influenza A virus.
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PMID:Sialidase activity in rimantadine-resistant and -sensitive influenza A viruses. 210

Synthetic thioglycoside-analogs of gangliosides such as Neu5Ac alpha(2-S-6)Glc beta(1-1)Ceramide (1) and the GM3 analog Neu5Ac alpha(2-S-6)Gal beta(1-4)Glc beta(1-1)Ceramide (2), competitively inhibited GM3 hydrolysis by the sialidase of different subtypes of human and animal influenza viruses with an apparent Ki value of 2.8 x 10(-6) and 1.5 x 10(-5) M, respectively. The inhibitory activity of the ganglioside GM4 analog [Neu5Ac alpha(2-S-6)Gal beta(1-1)Ceramide (3)], in which the glucose of 1 was substituted by galactose, was lower than that of 1 (Ki = 1.0 x 10(-4) M). The thioglycoside-analogs (1, 2, 3) of the gangliosides were non-hydrolyzable substrates for influenza virus sialidase. The inhibitory activity of 1 to bacterial sialidases from Clostridium perfringens and Arthrobacter ureafaciens was considerably lower than that to influenza virus sialidase, indicating that the structure of the active site in bacterial and influenza virus sialidase may be different and the analogs may be useful to determine the orientation of the substrate to the active site of sialidases, especially of influenza viruses.
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PMID:New ganglioside analogs that inhibit influenza virus sialidase. 213 50

Flavonoids (103 species) were tested for inhibitory activity against influenza virus sialidase using sodium p-nitrophenyl-N-acetyl-alpha-D-neuraminate as substrate. 5,7,4'-Trihydroxy-8-methoxyflavone from the root of Scutellaria baicalensis showed the most potent activity (IC50, 55 microM), and this flavone appeared to be a non-competitive inhibitor of the enzyme. Whereas, negligible or weak inhibitory activities were observed for mouse liver sialidase, beta-galactosidase and alpha-mannosidase as tested. This flavone also inhibited the infection by influenza virus A/PR/8/34 of Madin-Darby canine kidney cells, and replication of the virus in the allantoic sack of embryonated egg. These results suggest that flavone, which has potent influenza virus sialidase inhibitory activity, may have anti-influenza virus activity.
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PMID:Inhibition of influenza virus sialidase and anti-influenza virus activity by plant flavonoids. 239 58

The nature of the receptor-destroying enzyme (RDE) of influenza C virus has been elucidated by analyzing its effect on the haemagglutination inhibitors rat alpha 1-macroglobulin (RMG) and bovine submandibulary mucin (BSM), respectively. The inhibitory activity of both compounds is abolished by incubation with influenza C virus. After inactivation, RMG and BSM were found to contain reduced amounts of N-acetyl-9-O-acetylneuraminic acid (Neu5,9Ac2) and increased amounts of N-acetylneuraminic acid (Neu5Ac). H.p.l.c. analysis revealed that purified Neu5,9Ac2 is converted to Neu5Ac by incubation with influenza C virus. These results demonstrate that RDE of influenza C virus is neuraminate-O-acetylesterase [N-acyl-9(4)-O-acetylneuraminate O-acetylhydrolase (EC 3.1.1.53)]. The data also indicate that haemagglutination-inhibition (HI) by RMG and BSM and most likely virus attachment to cell surfaces involves binding of influenza C virus to Neu5,9Ac2.
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PMID:The receptor-destroying enzyme of influenza C virus is neuraminate-O-acetylesterase. 241 39

Histamine release from human basophils was investigated in vitro after removal of cell membrane sialic acid by three different sialidases. Pretreatment of the cells with sialidases from Cl. Perfringens, V. Cholera or Influenza virus A2 enhanced histamine release induced by subsequent stimulation of the cells with anti-IgE or the plant lectin Concanavalin A and caused a shift to the left of the dose-response curve for anti-IgE. The enhanced histamine release was reflected in a increased calcium sensitivity, thus suggesting that cell membrane sialic acid might be involved in the calcium fluxes preceeding histamine release. In higher doses the sialidase from Cl. Perfringens caused the cells to release histamine by itself, whereas the sialidases from V. Cholera and Influenza virus A2 in high doses inhibited the cell response to Concanavalin A.
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PMID:Enhancement of histamine release from human basophils pretreated with different sialidases. 242 28

Bacterial neuraminidases destroy influenza C virus receptors of chick erythrocytes and inactivate hemagglutination inhibitors: rat alpha 1-macroglobulin (RMG) and bovine submaxillary mucin (BSM). These data indicate that neuraminic acid may be a component of influenza C virus receptor. The inhibiting activity of RMG and BSM is also eliminated by the receptor-destroying enzyme (RDE) of influenza C virus. After inactivation, the inhibitors (RMG and BSM) contain a reduced amount of N-acetyl-9-0-acetylneuraminic acid (Neu5, 9Ac2) and a larger amount of N-acetylneuraminic acid (Neu5 Ac). Transformation of Neu5, 9Ac2 into Neu5 Ac may also occur upon incubation of free neuraminic acid with influenza C virus. These data indicate that the RDE of influenza C virus is neuraminate-O-acetylesterase (N-acyl-9 4-O-acetylneuraminate O-acetylhydrolase (EC 3.1.1.53). It was shown that inhibition of influenza C virus hemagglutination by RMG and BSM and, apparently, adhesion of the virus to the cell surface involves binding of influenza C virus with Neu5, 9Ac2.
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PMID:[The nature of the influenza C virus receptor and the specificity of the receptor-destroying enzyme]. 244 6

The unique properties of equine and guinea pig sera which make them potent inhibitors of influenza virus adsorption and infection have been investigated. The inhibitory activities of both sera are found to reside entirely in their respective alpha 2-macroglobulins, high molecular weight glycoproteins which bind to viral hemagglutinins via sialic acids of their N-linked carbohydrate groups. Structure analysis has shown that both proteins contain 4-O-acetyl-N-acetylneuraminic acid (4-O-Ac-NeuAc) (Hanaoka, K., Pritchett, T. J., Takasaki, S., Kochibe, N., Sabesan, S., Paulson, J.C., and Kobata, A. (1989) J. Biol. Chem. 264, 9842-9849). These 4-O-acetylated sialic acids have been found in few species, making their coincidence with high inhibitory potency in equine and guinea pig alpha 2-macroglobulin striking. However, 4-O-Ac-NeuAc does not appear to increase the avidity of interaction with influenza virus since isolated oligosaccharides of equine alpha 2-macroglobulin are no more potent inhibitors of adsorption than isolated oligosaccharides of human alpha 2-macroglobulin, which is a relatively poor inhibitor and contains only NeuAc. Since 4-O-Ac-NeuAc is resistant to cleavage by viral sialidase it may serve to protect the inhibitor from inactivation. These and supporting results suggest that the key property of equine and guinea pig alpha 2-macroglobulin which make them high potency inhibitors is a spatial arrangement of sialic acid containing oligosaccharide groups which allows optimal interaction with multiple hemagglutinins. The implications of these results for the design of low molecular weight inhibitors of influenza virus infection are discussed.
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PMID:Basis for the potent inhibition of influenza virus infection by equine and guinea pig alpha 2-macroglobulin. 247 Jul 65

Sialidase of influenza virus type A has been extensively studied through structural and kinetic approaches. However, sialidase of influenza virus type B has been less investigated. In this work, we have studied the activity and some properties (optimal pH, KM, Vmax, thermal stability) of sialidase in three influenza virus strains of type B (circulating in the period 1983-86) and also the activity and properties of sialidase from three virus strains of type A circulating at the same period of time. The results show that the activity and the Vmax was always higher for sialidase of type A viruses relative to those values of type B. Differences were also found for optimal pH and, in some cases, for thermal stability of the sialidase between strains belonging to the influenza viruses type A and B. However, the behaviour for the sialidase in all strains was very similar towards two competitive inhibitors. Thus, it could be suggested that the evolution pattern of the sialidase of both types of influenza viruses determines some modifications which result in a higher efficiency for sialidase of some strains of influenza virus type A, but maintaining in the two types of viruses a similar behaviour towards competitive inhibitors.
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PMID:Kinetic studies on the sialidase of three influenza B and three influenza A virus strains. 253 86


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