Sialidase active sites

The sialidase active site contains a relatively high number of charged amino acids and, in total, there are ten polar (Arg/Asp/Glu) and four non-polar residues that... 

Fig. 4 The influenza A viras sialidase active site showing some key interactions...

Analysis of Potential Binding Interactions within the Influenza Virus Sialidase Active Site... 

Fig. 7 The influenza virus A sialidase active site showing the five potential inhibitor binding subsites (with S5 containing the hydrophobic pocket formed by reorientation of the Glu276 side-chain), with oseltamivir carboxylate 18 placed in the active site...

An interesting feature of the influenza virus sialidase active site that offers the potential for developing inhibitors specific for N1 sialidases, including avian influenza A/H5N1 virus sialidase, has recently been revealed by X-ray crystallography. The... 

Viruses that contain amino acid substitutions in the sialidase that impart resistance to the developed inhibitors have been isolated from serial passage of virus in the presence of drug in cell culture and from the clinical setting (reviewed in McKimm-Breschkin 2000 Zambon and Hayden 2001 Cinatl et al. 2007a Reece 2007). In addition, influenza B virus variants with reduced drug sensitivity have been isolated from previously untreated patients (Hurt et al. 2006 Hatakeyama et al. 2007). The types of mutations that are observed are sub-type specific. The mutations present in variants isolated from clinical samples are shown in Table 1, and their locations within the sialidase active site are shown diagrammatically in Fig. 9. 

Fig. 3. A schematic representation of some key interactions of Neu5Ac2en 5 with conserved influenza virus A sialidase active site residues.

To facilitate the description of the binding between a-Neu5Ac and NA, the influenza virus sialidase active site can be divided into five regions (Fig. 17.7) [31,69], Subsite 1... 

FIGURE 17.12 Interaction of oseltamivir carboxylate (20) with the influenza virus sialidase active site. 

FIGURE 17.16 Comparison of group 1 and group 2 sialidase active sites, (a) Oseltamivir carboxylate binds into the open catalytic site of group 1 sialidase Nl. (b) Binding between oseltamivir carboxylate and group 2 sialidase N9 with the closed 150-loop. 

Structure of the sialidase active site with sialic acid bound, showing the region of the pocket with space for fitting an extra group to the right of the molecule. The blue net is a van der Waals surface and indicates the accessible surface of the cavity. 

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