Non-Viral Sialidases

A similar situation to that with the lytic transglycosylases occurs with a leech sialidase (sialidase L), which gives 2,7-anhydro-A-acetylneuraminic acid, despite being in GH 33 like all other non-viral sialidases and transialidases. This enzyme binds a C-glycoside substrate-analogue (aNeuNAc-CH2-CH=CH2) and product in the conformation. The conformation of glycosyl-enzyme... 

Influenza virus neuraminidases/Non-viral sialidases/Paraniyxovirus... 

The non-viral sialidases show a large sequence divergence (Figure 1) and a large range of sizes, 40-50 kDa in size, similar to that of the viral enzymes, up to over... 

The RIP and Asp-box motifs allow the prediction of the location of the catalytic domain in other large non-viral sialidases (Figure 4). Lack of sequence identity with other domains of known function does not allow prediction of the roles of the additional domains in many other large sialidases, however they too are likely to have carbohydrate-binding functionality. 

Marine sponges contain a host of bioactive compounds, particularly small molecules, and also contain a range of peptides that are non-ribosomally synthesised, often containing non-native amino acids. However, there are examples of peptides of ribosomal origin, including, for example, asteropine A isolated from the sponge Asteropus simplex.133 This peptide comprises 36 residues and three disulphide bonds. It has potent sialidase inhibitory activity and thus has applications in the design of novel viral inhibitors. Structural analysis of asteropine A with NMR spectroscopy revealed a cystine-knot motif, similar to that already described for plant toxins. This observation emphasises the fact that the cystine-knot motif is extremely prevalent in disulphide-rich peptides.134 Asteropine A, discovered in 2006, was the first reported cystine-knot peptide isolated from marine invertebrates other than from cone snails, which are described in more detail below. 

Table 4. The influence of inhibitors on viral, bacterial and mammalian sialidases The strength of inhibition is indicated as weak (+) to very strong (-h + -H) or no inhibition (—). High (H) and low (L) molecular weight inhibitors are indicated and inhibition as competitive (C) or non-competitive (NC). ND, not determined... 

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