Substrate specificity of neuraminidases

Drzeniek, R.

doi:10.1007/bf01004994

Cited by 166 publications

(68 citation statements)

References 82 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…They vary greatly from one another in substrate specificity and enzyme kinetics. Among them, the large bacterial sialidases tend to be the more robust enzymes (1,8,11). Among the large bacterial sialidases, such as the ones from Arthrobacter ureafaciens, Clostridium perfringens, V. cholerae, and Actinomyces viscosus, the catalytic domain of A. viscosus sialidase was selected as the sialidase component of the novel therapeutic candidate for influenza based on three criteria: (i) A. viscosus sialidase has broad substrate specificity (54); (ii) it has one of the highest specific activities reported (54); and (iii) it should be well tolerated by the human immune system because A. viscosus is a part of the normal oral and gastrointestinal flora in humans (53) which normally exposes the human mucosal surface to the sialidase.…”

Section: Influenza Caused By Infection With Influenza Virus a (Ifvmentioning

confidence: 99%

Sialidase Fusion Protein as a Novel Broad-Spectrum Inhibitor of Influenza Virus Infection

Malakhov¹,

Aschenbrenner²,

Smee

et al. 2006

Antimicrob Agents Chemother

213

214

View full text Add to dashboard Cite

Influenza is a highly infectious disease characterized by recurrent annual epidemics and unpredictable major worldwide pandemics. Rapid spread of the highly pathogenic avian H5N1 strain and escalating human infections by the virus have set off the alarm for a global pandemic. To provide an urgently needed alternative treatment modality for influenza, we have generated a recombinant fusion protein composed of a sialidase catalytic domain derived from Actinomyces viscosus fused with a cell surface-anchoring sequence. The sialidase fusion protein is to be applied topically as an inhalant to remove the influenza viral receptors, sialic acids, from the airway epithelium. We demonstrate that a sialidase fusion construct, DAS181, effectively cleaves sialic acid receptors used by both human and avian influenza viruses. The treatment provides long-lasting effect and is nontoxic to the cells. DAS181 demonstrated potent antiviral and cell protective efficacies against a panel of laboratory strains and clinical isolates of IFV A and IFV B, with virus replication inhibition 50% effective concentrations in the range of 0.04 to 0.9 nM. Mouse and ferret studies confirmed significant in vivo efficacy of the sialidase fusion in both prophylactic and treatment modes.

show abstract

Section: Influenza Caused By Infection With Influenza Virus a (Ifvmentioning

confidence: 99%

Sialidase Fusion Protein as a Novel Broad-Spectrum Inhibitor of Influenza Virus Infection

Malakhov¹,

Aschenbrenner²,

Smee

et al. 2006

Antimicrob Agents Chemother

213

214

View full text Add to dashboard Cite

show abstract

“…In addition, viral neuraminidases specifically hydrolyse the different types of a-ketosidic linkage between N-acetylneuraminic acid and adjacent carbohydrate molecules. The nature of this carbohydrate is of minor importance for the recognition by these enzymes, but large substituents on these carbohydrates make such compounds resistant towards bacterial and viral neuraminidases owing to steric hindrance (Drzeniek, 1973). However, we have observed that the chemically sulphated sialoglycopeptides inhibited the hydrolysis of N-acetylneuraminic acid from N-acetylneuraminyl-lactose, bovine submaxillarygland mucin and from the native sialoglycopeptides by steric hindrance (Mian et al, 1979).…”

mentioning

confidence: 58%

“…The specificity of neuraminidase towards 0. values between 3 and 5.6 by using 0.05M-Na2HPO4/ citric acid buffers and at pH values between 5.8 and 8.0 by using 0.05 M-Na2HPO4/NaH2PO4 buffers (Gomori, 1955 1979 different types of linkage between N-acetylneuraminic acid and the lactosyl moiety of the compound, i.e. (2->3)-, (2-*4)-and (2->6) isomers has been tested previously (for review see Drzeniek, 1973). Previously reported data show that C. perfringens (Cassidy et al, 1965), Vibrio cholerae (Drzeniek, 1967;Drzeniek & Gauhe, 1970) and liver neuraminidases (Horvat & Touster, 1968) hydrolysed Nacetylneuraminyl-(2--6)-lactose half as fast as N-acetylneuraminyl-(2--3)-lactose.…”

Section: Assay Of Lactase Activitymentioning

confidence: 99%

“…Bacterial and viral neuraminidases recognize substituents on the N-acetylneuraminic acid molecule. The resistance to hydrolysis by neuraminidase of substances containing the substituted N-acetylneuraminic acid molecule have been a subject of great interest from the point of view of specificity of enzyme action (for review see Drzeniek, 1973). In addition, viral neuraminidases specifically hydrolyse the different types of a-ketosidic linkage between N-acetylneuraminic acid and adjacent carbohydrate molecules.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Effect of O-sulphate groups in lactose and N-acetylneuraminyl-lactose on their enzymic hydrolysis

Mian¹,

Anderson²,

Kent³

1979

Biochemical Journal

View full text Add to dashboard Cite

show abstract

“…One common type of substitution responsible for such diversity is that of an 0-acetyl ester on the exocyclic (7/8/9) side chain of the molecule. These substitutions could affect the conformation of the parent molecule and clearly have significant effects on enzyme function (3)(4)(5)(6), complement activation (7) and virus binding (8), and on the antigenicity of gangliosides (9)(10)(11) and bacterial polysaccharides (12). There is also evidence for developmental regulation of these substitutions in tissues as diverse as embryonic brain (11) and neonatal colonic mucosa (13).…”

mentioning

confidence: 99%

A sialic acid-specific O-acetylesterase in human erythrocytes: possible identity with esterase D, the genetic marker of retinoblastomas and Wilson disease.

Varki¹,

Muchmore²,

Díaz³

1986

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

The "nonspecific" esterases are a family of enzymes that were originally identified because of their reaction with synthetic 0-acetyl ester substrates. While the electrophoretic polymorphisms of these enzymes have been extremely useful for genetic studies, their biological functions have remained completely unknown. Esterase D is characterized by its reactivity with 4-methylumbeiliferyl acetate. This enzyme has recently been of particular interest because of its tight linkage to the putative recessive gene causing retinoblastomas, and to the recessive gene causing Wilson disease. We describe here the partial purification of a human erythrocyte esterase that appears to be highly specific for O-acetylated sialic acids. We next present evidence that suggests that esterase D is identical to this sialic acid-specific O-acetylesterase. First, both activities copurify from human erythrocyte lysates through several different purification steps, each of which use different principles of separation. Second, both activities show a remarkably similar proffle of inhibition with a variety ofdifferent agents. Third, they both show a nearly identical heat-inactivation profile. This cytosolic sialic acid-specific O-acetylesterase appears to be involved in the "recycling" of O-acetylated sialic acid molecules. Thus, esterase D may be the first nonspecific esterase for which a specific biological role can be predicted.The sialic acids are a family of N-and 0-substituted derivatives of N-acetylneuraminic acid (1, 2).t While a great deal has been written about the sialic acids and their probable biological functions, many studies fail to take into account the extent of diversity in these molecules. One common type of substitution responsible for such diversity is that of an 0-acetyl ester on the exocyclic (7/8/9) side chain of the molecule. These substitutions could affect the conformation of the parent molecule and clearly have significant effects on enzyme function (3-6), complement activation (7) and virus binding (8), and on the antigenicity of gangliosides (9-11) and bacterial polysaccharides (12). There is also evidence for developmental regulation of these substitutions in tissues as diverse as embryonic brain (11) and neonatal colonic mucosa (13). However, the exact biological roles of these substitutions are currently unknown.We have been studying the biosynthesis and reutilization of such 0-acetylated sialic acids in various systems (13)(14)(15) (26). The Dowex-50 beads were removed by passing over a glass wool filter and the methanolic acid was removed by evaporation. The residue was fractionated by preparative paper chromatography on Whatman 3MM paper in n-butanol/acetic acid/water (4:1:5, upper phase). Strips (1 cm) were cut, soaked in 50% methanol, and aliquots were counted. The major peak with an Rf of 0.58 was pooled, dried, saponified with 3 ml of 2 M NH40H for 2 hr at 100°C, dried again, and subjected to paper chromatography in the same system. The major peak was again pooled (j3-methylglycoside) and the si...

show abstract

Substrate specificity of neuraminidases

Cited by 166 publications

References 82 publications

Sialidase Fusion Protein as a Novel Broad-Spectrum Inhibitor of Influenza Virus Infection

Sialidase Fusion Protein as a Novel Broad-Spectrum Inhibitor of Influenza Virus Infection

Effect of O-sulphate groups in lactose and N-acetylneuraminyl-lactose on their enzymic hydrolysis

A sialic acid-specific O-acetylesterase in human erythrocytes: possible identity with esterase D, the genetic marker of retinoblastomas and Wilson disease.

Contact Info

Product

Resources

About