Molecular Modeling Studies on Ligand Binding to Sialidase from Influenza Virus and the Mechanism of Catalysis

Taylor, N. Seddon; M, von Itzstein

doi:10.1021/jm00031a011

Cited by 208 publications

(160 citation statements)

References 18 publications

(35 reference statements)

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“…Amino acid positions 150 and 151 are located in the 150-loop (residues 147-152) at the edge of the catalytic site [24,25]. However, residue 151, unlike residue 150, is categorized as a catalytic site residue and is believed to stabilize the transition state intermediate [26]. The position of these residues in or close to the catalytic site and the inhibition of NAmediated binding by oseltamivir suggest that the binding of NA to turkey erythrocytes is mediated via the catalytic site and not via haemadsorption sites, which are secondary sialic acid-binding sites that have been described for some avian NAs [27][28][29][30][31].…”

Section: Discussionmentioning

confidence: 99%

Neuraminidase-mediated haemagglutination of recent human influenza A(H3N2) viruses is determined by arginine 150 flanking the neuraminidase catalytic site

Mögling

Richard

Vliet

et al. 2017

Journal of General Virology

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Over the last decade, an increasing proportion of circulating human influenza A(H3N2) viruses exhibited haemagglutination activity that was sensitive to neuraminidase inhibitors. This change in haemagglutination as compared to older circulating A(H3N2) viruses prompted an investigation of the underlying molecular basis. Recent human influenza A(H3N2) viruses were found to agglutinate turkey erythrocytes in a manner that could be blocked with either oseltamivir or neuraminidase-specific antisera, indicating that agglutination was driven by neuraminidase, with a low or negligible contribution of haemagglutinin. Using representative virus recombinants it was shown that the haemagglutinin of a recent A(H3N2) virus indeed had decreased activity to agglutinate turkey erythrocytes, while its neuraminidase displayed increased haemagglutinating activity. Viruses with chimeric and mutant neuraminidases were used to identify the amino acid substitution histidine to arginine at position 150 flanking the neuraminidase catalytic site as the determinant of this neuraminidase-mediated haemagglutination. An analysis of publicly available neuraminidase gene sequences showed that viruses with histidine at position 150 were rapidly replaced by viruses with arginine at this position between 2005 and 2008, in agreement with the phenotypic data. As a consequence of neuraminidase-mediated haemagglutination of recent A(H3N2) viruses and poor haemagglutination via haemagglutinin, haemagglutination inhibition assays with A(H3N2) antisera are no longer useful to characterize the antigenic properties of the haemagglutinin of these viruses for vaccine strain selection purposes. Continuous monitoring of the evolution of these viruses and potential consequences for vaccine strain selection remains important.

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Section: Discussionmentioning

confidence: 99%

Neuraminidase-mediated haemagglutination of recent human influenza A(H3N2) viruses is determined by arginine 150 flanking the neuraminidase catalytic site

Mögling

Richard

Vliet

et al. 2017

Journal of General Virology

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“…Protonation is favoured by the relatively negative O(2 -1) atom (2 0.7). This ion represents a Neu5Ac transition state analogue in the sialidase reactions, having a distorted chair conformation [38,39]. It can bind a hydroxyl from a water molecule leading to free Neu5Ac.…”

Section: Sialidase and Trans-sialidasementioning

confidence: 99%

Ab initio calculations on various sialic acids provide valuable information about sialic acid-specific enzymes

Lenthe

Boer

Havenith

et al. 2004

Journal of Molecular Structure: THEOCHEM

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This study presents ab initio calculations on six sialic acid derivatives (N-acetylneuraminic acid, 2-deoxy-2,3-didehydro-Nacetylneuraminic acid, N-acetyl-4-O-acetylneuraminic acid, N-glycolylneuraminic acid, N-glycolyl-4-O-acetylneuraminic acid and N-acetyl-9-O-acetylneuraminic acid). The calculations were carried out using the GAMESS-UK-Program. Since the charge distribution of a ligand has an essential impact on the specific interaction with an enzyme or a receptor, the precise results of ab initio calculations lead to significant information concerning possible roles of the different functional groups occurring on sialic acids. In correlation to this, valuable conclusions about the activities of different sialic acid-specific enzymes, such as sialidases, trans-sialidases, lyases and O-acetyl-or O-methyltransferases can be drawn, since these activities strongly depend on the presence or absence of the various functional groups. q 2004 Published by Elsevier B.V.

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“…All of these current NA inhibitors were designed based upon the structure of 2-deoxy-2,3-didehydro-N-acetylneuraminic acid (Neu5Ac2en), a putative NA transition-state analogue 8,[10][11][12] . Insight into the NA catalytic mechanism and the proposed oxocarbenium ion transition-state intermediate were crucial for the design of Neu5Ac2en analogues with potent NA inhibitory activity 13,14 . However, evidence regarding the key influenza NA catalytic residues has remained elusive and the successful design of highly effective next-generation influenza NA inhibitors has proven to be a difficult task.…”

mentioning

confidence: 99%

Influenza neuraminidase operates via a nucleophilic mechanism and can be targeted by covalent inhibitors

et al. 2013

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Molecular Modeling Studies on Ligand Binding to Sialidase from Influenza Virus and the Mechanism of Catalysis

Cited by 208 publications

References 18 publications

Neuraminidase-mediated haemagglutination of recent human influenza A(H3N2) viruses is determined by arginine 150 flanking the neuraminidase catalytic site

Neuraminidase-mediated haemagglutination of recent human influenza A(H3N2) viruses is determined by arginine 150 flanking the neuraminidase catalytic site

Ab initio calculations on various sialic acids provide valuable information about sialic acid-specific enzymes

Influenza neuraminidase operates via a nucleophilic mechanism and can be targeted by covalent inhibitors

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