Structural model sialic acid

Figure 5.24 Space-filling model (green) of the sialic acid binding domain of hemagglutinin with a bound inhibitor (red) Illustrating the different binding grooves. The sialic acid moiety of the Inhibitor binds in the central groove. A large hydrophobic substituent, Ri, at the Cz position of sialic acid binds in a hydrophobic channel that runs from the central groove to the bottom of the domain. (Adapted from S.J. Watowich et al.. Structure 2 719-731, 1994.)...

Such studies, and others on an O-phosphonomannan155 and a tei-choic acid,168 relied on judicious comparisons (of shift) with signals of model compounds, and these are simpler than conventional, analytical procedures. For example, it is difficult to methylate alkali-labile O-phosphonomannans, and sialic acid and KDO-containing polymers would require difficultly available, O-methylated standards. In addition, periodate-oxidation analyses are restricted to polymers having fortuitously amenable, chemical structures. 

The neuraminidases together with gangliosides have been localized in the nerve ending structures (6, 7 ). Theoretically the sialylation and desialylation cycle may mediate a cyclic reaction at a very important locale in a nerve synaptic structure. This hypothetical involvement of sialic acid metabolism in synaptic transmission has gained support from several studies which have suggested a synaptic localization of the glycosyltransferases (8, 9,10,11) and from proposed theoretical models in which the sialo-glycolipids are considered an important constituent in the functional units of neuronal membranes (12,13,14). 

Fig. 19. Model of sialic acid structural features required for the interaction with sialate lyase and binding of inhibitors. Based on data from ref. [892].

It was originally conceived through the application of modelling techniques to the crystal structure of influenza virus NA complexed with sialic acid [34,38]. 

Figure35 Model representations of sialic-acid-conjugated polymeric inhibitor subunits used to inhibit viral infection. Structures are not drawn to scale. (Courtesy of Bioconjugate Chem. 1999, (10)2, 273. Copyright 1999 American Chemical Society.)...

Fig. 1 Sialic acid binding sites of the hemagglutinin (a) and the neuraminidase (b) of influenza A virus and the hemagglutinin-esterase-fusion protein of influenza C virus (c). Molecular surfaces of HA and HEF trimers and the NA tetramer are shown. Receptor-binding sites of HA, HEF and the hemadsorption site of NA are colored ye/tow. The catalytic sites of NA and HEF are colored green. Sialic acid moieties in the binding sites of HA and NA are shown as stick models. The figtffe is based on crystal structures IMQM, 1W20, and IFLC from Protein Data Bank...

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