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Role of Secondary Sialic Acid Binding Sites in Influenza N1 Neuraminidase

[Image: see text] Within influenza viral particles, the intricate balance between host cell binding and sialic acid receptor destruction is carefully maintained by the hemagglutinin (HA) and neuraminidase (NA) glycoproteins, respectively. A major outstanding question in influenza biology is the func...

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Autores principales: Sung, Jeffrey C., Wynsberghe, Adam W. Van, Amaro, Rommie E., Li, Wilfred W., McCammon, J. Andrew
Formato: Texto
Lenguaje:English
Publicado: American Chemical Society 2010
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2835425/
https://www.ncbi.nlm.nih.gov/pubmed/20155919
http://dx.doi.org/10.1021/ja9073672
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author Sung, Jeffrey C.
Wynsberghe, Adam W. Van
Amaro, Rommie E.
Li, Wilfred W.
McCammon, J. Andrew
author_facet Sung, Jeffrey C.
Wynsberghe, Adam W. Van
Amaro, Rommie E.
Li, Wilfred W.
McCammon, J. Andrew
author_sort Sung, Jeffrey C.
collection PubMed
description [Image: see text] Within influenza viral particles, the intricate balance between host cell binding and sialic acid receptor destruction is carefully maintained by the hemagglutinin (HA) and neuraminidase (NA) glycoproteins, respectively. A major outstanding question in influenza biology is the function of a secondary sialic acid binding site on the NA enzyme. Through a series of Brownian dynamics (BD) simulations of the avian N1, human pandemic N2, and currently circulating pandemic (H1)N1 enzymes, we have probed the role of this secondary sialic acid binding site in the avian N1 subtype. Our results suggest that electrostatic interactions at the secondary and primary sites in avian NA may play a key role in the recognition process of the sialic acid receptors and catalytic efficiency of NA. This secondary site appears to facilitate the formation of complexes with the NA protein and the sialic acid receptors, as well as provide HA activity to a lesser extent. Moreover, this site is able to steer inhibitor binding as well, albeit with reduced capacity in N1, and may have potential implications for drug resistance or optimal inhibitor design. Although the secondary sialic acid binding site has previously been shown to be nonconserved in swine NA strains, our investigations of the currently circulating pandemic H1N1 strain of swine origin appears to have retained some of the key features of the secondary sialic acid binding site. Our results indicate possible lowered HA activity for this secondary sialic acid site, which may be an important event in the emergence of the current pandemic strain.
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spelling pubmed-28354252010-03-11 Role of Secondary Sialic Acid Binding Sites in Influenza N1 Neuraminidase Sung, Jeffrey C. Wynsberghe, Adam W. Van Amaro, Rommie E. Li, Wilfred W. McCammon, J. Andrew J Am Chem Soc [Image: see text] Within influenza viral particles, the intricate balance between host cell binding and sialic acid receptor destruction is carefully maintained by the hemagglutinin (HA) and neuraminidase (NA) glycoproteins, respectively. A major outstanding question in influenza biology is the function of a secondary sialic acid binding site on the NA enzyme. Through a series of Brownian dynamics (BD) simulations of the avian N1, human pandemic N2, and currently circulating pandemic (H1)N1 enzymes, we have probed the role of this secondary sialic acid binding site in the avian N1 subtype. Our results suggest that electrostatic interactions at the secondary and primary sites in avian NA may play a key role in the recognition process of the sialic acid receptors and catalytic efficiency of NA. This secondary site appears to facilitate the formation of complexes with the NA protein and the sialic acid receptors, as well as provide HA activity to a lesser extent. Moreover, this site is able to steer inhibitor binding as well, albeit with reduced capacity in N1, and may have potential implications for drug resistance or optimal inhibitor design. Although the secondary sialic acid binding site has previously been shown to be nonconserved in swine NA strains, our investigations of the currently circulating pandemic H1N1 strain of swine origin appears to have retained some of the key features of the secondary sialic acid binding site. Our results indicate possible lowered HA activity for this secondary sialic acid site, which may be an important event in the emergence of the current pandemic strain. American Chemical Society 2010-02-15 2010-03-10 /pmc/articles/PMC2835425/ /pubmed/20155919 http://dx.doi.org/10.1021/ja9073672 Text en Copyright © 2010 American Chemical Society http://pubs.acs.org This is an open-access article distributed under the ACS AuthorChoice Terms & Conditions. Any use of this article, must conform to the terms of that license which are available at http://pubs.acs.org.
spellingShingle Sung, Jeffrey C.
Wynsberghe, Adam W. Van
Amaro, Rommie E.
Li, Wilfred W.
McCammon, J. Andrew
Role of Secondary Sialic Acid Binding Sites in Influenza N1 Neuraminidase
title Role of Secondary Sialic Acid Binding Sites in Influenza N1 Neuraminidase
title_full Role of Secondary Sialic Acid Binding Sites in Influenza N1 Neuraminidase
title_fullStr Role of Secondary Sialic Acid Binding Sites in Influenza N1 Neuraminidase
title_full_unstemmed Role of Secondary Sialic Acid Binding Sites in Influenza N1 Neuraminidase
title_short Role of Secondary Sialic Acid Binding Sites in Influenza N1 Neuraminidase
title_sort role of secondary sialic acid binding sites in influenza n1 neuraminidase
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2835425/
https://www.ncbi.nlm.nih.gov/pubmed/20155919
http://dx.doi.org/10.1021/ja9073672
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