Sialyltransferases specificity

Replacement of A-acyl and 0-acyl by A-thioacyl groups in sialo-sugar chains of cell surface glycoproteins can influence certain biological functions mediated by sialic acids, such as cellular adhesion phenomena or virus specificity for host cells. Interestingly, sialyltransferases specific for different... 

At present little detailed evidence is available for sialyltransferases specifically involved in membrane glycoprotein biosynthesis. It is probable that the membrane-bound sialyltransferase specificities described for glycoproteins (sections III. 3 and III.4) and glycolipids (section III. 5) will be similar, as the structures of membrane complex carbohydrates show the same features found in soluble molecules (e.g. Kobata 1979, Rauvala and Finne 1979, Montreuil 1980). Much indirect evidence has come from cell culture studies, frequently in studies on normal and transformed or malignant cells (Hughes 1976, Harmon 1978, Kottgen et al. 1979). 

Cytidine 5 -phospho-A-acetylneuraminate (298), the coenzyme of sialyltransferases, is a sugar-nucleotide in which the leaving group is a nucleotidyl monophosphate that contains a carboxylate group directly attached to the anomeric centre. Studies of its hydrolysis reveal that at pH 5 specific acid catalysis occurs (Scheme 34) to yield a glycosyl carbocation as a tight ion pair, the lifetime of which was estimated... 

In the earlier studies, complete purification of sialyltransferases had not been achieved, but this did not preclude the possibility of the presence of more than one sialyltransferase in an enzyme preparation, and it prevented detailed study of the molecular properties of these enzymes. This is why the results from the former studies on the specificity of substrates must be interpreted with care. Exact studies of si-... 

Substrate-specificity studies on microsomal, frog-liver sialyltrans-ferase revealed the presence of (2—>3) and (2—>6) activities.277 This enzyme system readily sialylates oligosaccharides, but is almost inactive with asialofetuin, which is in contrast to the sialylation of oligosaccharides, as well as asialofetuin, by rat-liver sialyltransferase.278 The conclusion from this observation is that acceptor specificity of sialyl-transferases isolated from liver of evolutionary distant animals is similar for substrates of low molecular weight, but differs for compounds of high molecular weight.279... 

Specificity and Membrane Properties of Young Rat Brain Sialyltransferases... 

It is interesting that all four reactions studied gave the same apparent Km values for CMP-NeuNAc. This observation suggests that the CMP-NeuNAc binding sites of the different species of sialyltransferases are similar in structure and affinity properties, although the binding sites for the acceptors and the catalytic sites may be very different, providing a basis for substrate specificities. 

It is conceivable that the natural receptor binding structure for Sendai virus has only one terminal NeuAc residue, but it is also possible that some of the oligosaccharide moieties received a disialosyl linkage during the incubation with the specific sialyltransferase. 

Paulson, J.C. Sadler, J.E. Hill, R.L. Restoration of specific myxovirus receptors to asialoerythrocytes by incorporation of sialic acid with pure sialyltransferases. 

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