Sialidase, action

The internal, sialic acid residue of GMj or GM2 is readily susceptible to sialidase action after enzymic release of the peripheral Gal and GalNAc residues, leading to GM3 having a terminal sialyl residue, and this represents the natural pathway of the catabolism of ganglio-sides.110 354 355... 

Fig. 18. Amino acids essential for bacterial sialidase action. The positions of the amino acid residues interacting with different parts of the Neu5Ac molecule or forming a hydrophobic pocket (by Leu, Trp and Met indicated by a dotted line at the left side of the sialic acid molecule) are shown. Vc, Vibrio cholerae sialidase [791] St, Salmonella typhimurium sialidase [790] and Cp, Clostridium perfringens sialidase [R.G. Kleineidam, personal communication].

Acetylation of mucin-bound and membrane-bound sialic acids makes them more resistant towards sialidase action [8,33,245,853,854]. This may be one of the reasons why intestinal mucins, especially of the colon, are often O-acetylated (ref. [245], and section 8.4.2). The high level of 0-acetylation of sialic acids observed in the endothelia of blood vessels, e.g, in liver, detected by histochemical methods using influenza C virus hemagglutinin, is assumed to have a similar function [234,235,730]. 

The proposed mechanism for sialidase action (Scheme 22.1) involves an initial conformational change of the NeuSAc residue of the substrate upon binding in the active site, from the solution-dominant Cs chair conformation to an a-boat-like conformation (1, Scheme 22.1). Based on kinetic isotope effect... 

A further aspect of the wide range of substrates for sialidases has been the analysis of these substrates. The determination of oligosaccharide chain structures has allowed precise study of sialidase specificity. A need for a spectrum of well defined substrates has developed as a prerequisite for the elucidation of sialidase specificity. The large body of data which has accumulated on the sialidases points to a number of characteristics general to sialidase action, and forms the basis of current knowledge about sialidases. 

The influence of the C-7 to C-9 side chain of the sialic acid molecule on sialidase action has been demonstrated using complex carbohydrates subjected to mild periodate oxidation and subsequent borohydride reduction to yield C-7 and C-8 analogues of sialic acid. The progressive shortening of the chain led to a progressive decrease in bacterial and viral sialidase action (Suttajit and Winzler... 

Reduction of sialidase action Influence on glycosylation, e.g. polysiaiyiation, or branching... 

The presence of the free carboxyl group in the sialic acid residue is essential for sialidase action (Yu and Ledeen, 1969). The methyl esters of sialic acids in... 

Two major types of A-substituted sialic acids are found in natural sialogly-coconjugates A-acetyl and A-glycolylneuraminic acids. The former is usually more susceptible to sialidase than the A-glycolyl derivative (Corfield et al., 1981a,b). Synthetic derivatives with A-formyl, A-propionyl, or other groups with larger sizes have reduced or abolished susceptibility to sialidase action (Brossmer and Nebelin, 1969). 

The shortening of the C-7-C-9 side chain in a sialic acid residue generally renders it less susceptible to the sialidase action (Suttajit and Winzler, 1971 Veh et... 

Schengrund, C. L., and Rosenberg, A., 1972, Neuronal sialidase action in isolated nerve endings, in Third Annual Meeting of the American Society of Neurochemistry, Vol. 3, No. 1, pp. 118. 

Several workers have tried to ascertain the effects of mammalian sialidase action on endogenous substrates. Studies of the effects of soluble microbial sialidases on cell-surface properties and on the activities of sialocompounds have been performed in order to try to determine, by analogy, the role of mammalian sialidase. This part of the chapter will summarize what is known about mammalian, and where possible, avian sialidase and will suggest biological roles for the enzyme. 

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