FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2108157089> ?p ?o ?g. }

• W2108157089 endingPage "746" @default.
• W2108157089 startingPage "735" @default.
• W2108157089 abstract "Background: Inhibitors of the influenza virus neuraminidase have been shown to be effective antiviral agents in humans. Several studies have reported the selection of novel influenza strains when the virus is cultured with neuraminidase inhibitors in vitro. These resistant viruses have mutations either in the neuraminidase or in the viral haemagglutinin. Inhibitors in which the glycerol sidechain at position 6 of 2-deoxy-2,3-dehydro-N-acetylneuraminic acid (Neu5Ac2en) has been replaced by carboxamide-linked hydrophobic substituents have recently been reported and shown to select neuraminidase variants. This study seeks to clarify the structural and functional consequences of replacing the glycerol sidechain of the inhibitor with other chemical constituents.Results: The neuraminidase variant Arg292→Lys is modified in one of three arginine residues that encircle the carboxylate group of the substrate. The structure of this variant in complex with the carboxamide inhibitor used for its selection, and with other Neu5Ac2en analogues, is reported here at high resolution. The structural consequences of the mutation correlate with altered inhibitory activity of the compounds compared with wild-type neuraminidase.Conclusions: The Arg292→Lys variant of influenza neuraminidase affects the binding of substrate by modification of the interaction with the substrate carboxylate. This may be one of the structural correlates of the reduced enzyme activity of the variant. Inhibitors that have replacements for the glycerol at position 6 are further affected in the Arg292→Lys variant because of structural changes in the binding site that apparently raise the energy barrier for the conformational change in the enzyme required to accommodate such inhibitors. These results provide evidence that a general strategy for drug design when the target has a high mutation frequency is to design the inhibitor to be as closely related as possible to the natural ligands of the target." @default.
• W2108157089 created "2016-06-24" @default.
• W2108157089 creator A5013150107 @default.
• W2108157089 creator A5018240656 @default.
• W2108157089 creator A5028036443 @default.
• W2108157089 creator A5050138323 @default.
• W2108157089 creator A5051473344 @default.
• W2108157089 creator A5059198923 @default.
• W2108157089 creator A5089626651 @default.
• W2108157089 date "1998-06-01" @default.
• W2108157089 modified "2023-10-16" @default.
• W2108157089 title "Drug design against a shifting target: a structural basis for resistance to inhibitors in a variant of influenza virus neuraminidase" @default.
• W2108157089 cites W1576999979 @default.
• W2108157089 cites W1594139320 @default.
• W2108157089 cites W1784292360 @default.
• W2108157089 cites W1939857580 @default.
• W2108157089 cites W1957871368 @default.
• W2108157089 cites W1968632703 @default.
• W2108157089 cites W1969288438 @default.
• W2108157089 cites W1973864996 @default.
• W2108157089 cites W1974728866 @default.
• W2108157089 cites W1979188828 @default.
• W2108157089 cites W1980785974 @default.
• W2108157089 cites W1983490614 @default.
• W2108157089 cites W1995452398 @default.
• W2108157089 cites W2003926950 @default.
• W2108157089 cites W2004647290 @default.
• W2108157089 cites W2009296046 @default.
• W2108157089 cites W2016256869 @default.
• W2108157089 cites W2023133891 @default.
• W2108157089 cites W2025807461 @default.
• W2108157089 cites W2035897596 @default.
• W2108157089 cites W2039828671 @default.
• W2108157089 cites W2041411780 @default.
• W2108157089 cites W2049305582 @default.
• W2108157089 cites W2050306038 @default.
• W2108157089 cites W2051588573 @default.
• W2108157089 cites W2059734102 @default.
• W2108157089 cites W2059747050 @default.
• W2108157089 cites W2062503376 @default.
• W2108157089 cites W2065335184 @default.
• W2108157089 cites W2071138716 @default.
• W2108157089 cites W2079257001 @default.
• W2108157089 cites W2081408316 @default.
• W2108157089 cites W2086358466 @default.
• W2108157089 cites W2088195624 @default.
• W2108157089 cites W2113619184 @default.
• W2108157089 cites W2115959170 @default.
• W2108157089 cites W2116275717 @default.
• W2108157089 cites W2124234796 @default.
• W2108157089 cites W2129587690 @default.
• W2108157089 cites W2131644691 @default.
• W2108157089 cites W2137727873 @default.
• W2108157089 cites W2142671293 @default.
• W2108157089 cites W2151763773 @default.
• W2108157089 cites W2156658075 @default.
• W2108157089 cites W2163960578 @default.
• W2108157089 cites W2165607122 @default.
• W2108157089 cites W2168030379 @default.
• W2108157089 cites W2316985047 @default.
• W2108157089 cites W2334261876 @default.
• W2108157089 cites W2467227936 @default.
• W2108157089 cites W2484676188 @default.
• W2108157089 cites W4327670649 @default.
• W2108157089 cites W46402073 @default.
• W2108157089 doi "https://doi.org/10.1016/s0969-2126(98)00075-6" @default.
• W2108157089 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/9655825" @default.
• W2108157089 hasPublicationYear "1998" @default.
• W2108157089 type Work @default.
• W2108157089 sameAs 2108157089 @default.
• W2108157089 citedByCount "195" @default.
• W2108157089 countsByYear W21081570892012 @default.
• W2108157089 countsByYear W21081570892013 @default.
• W2108157089 countsByYear W21081570892014 @default.
• W2108157089 countsByYear W21081570892015 @default.
• W2108157089 countsByYear W21081570892016 @default.
• W2108157089 countsByYear W21081570892017 @default.
• W2108157089 countsByYear W21081570892018 @default.
• W2108157089 countsByYear W21081570892019 @default.
• W2108157089 countsByYear W21081570892020 @default.
• W2108157089 countsByYear W21081570892021 @default.
• W2108157089 countsByYear W21081570892022 @default.
• W2108157089 countsByYear W21081570892023 @default.
• W2108157089 crossrefType "journal-article" @default.
• W2108157089 hasAuthorship W2108157089A5013150107 @default.
• W2108157089 hasAuthorship W2108157089A5018240656 @default.
• W2108157089 hasAuthorship W2108157089A5028036443 @default.
• W2108157089 hasAuthorship W2108157089A5050138323 @default.
• W2108157089 hasAuthorship W2108157089A5051473344 @default.
• W2108157089 hasAuthorship W2108157089A5059198923 @default.
• W2108157089 hasAuthorship W2108157089A5089626651 @default.
• W2108157089 hasBestOaLocation W21081570891 @default.
• W2108157089 hasConcept C104317684 @default.
• W2108157089 hasConcept C134164806 @default.
• W2108157089 hasConcept C142724271 @default.
• W2108157089 hasConcept C159047783 @default.
• W2108157089 hasConcept C181199279 @default.
• W2108157089 hasConcept C185592680 @default.

• next