ArticleProceedings of the National Academy of Sciences of the United States of America2008
Amantadine-induced conformational and dynamical changes of the influenza M2 transmembrane proton channel.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 77 papers.
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Who cites it
77 citing papers in PubMed, 125 citations in OpenAlex.
- Orientation Selection in Proton-Detected Magic-Angle Spinning Torsion Angle Experiments.The journal of physical chemistry. A · 2026Article
- Article
- Molecular biophysics and inhibition mechanism of influenza virus A M2 viroporin by adamantane-based drugs - Challenges in designing antiviral agents.Journal of structural biology: X · 2025Article
- Solid-state NMR protocols for unveiling dynamics and (drug) interactions of membrane-bound proteins.Protein science : a publication of the Protein Society · 2025Article
- Solid-State NMR of Virus Membrane Proteins.Accounts of chemical research · 2025Article
- Differences in Oligomerization of the SARS-CoV-2 Envelope Protein, Poliovirus VP4, and HIV Vpu.Biochemistry · 2024Article
- Real-time tracking of drug binding to influenza A M2 reveals a high energy barrier.Journal of structural biology: X · 2023Article
- What's the defect? Using mass defects to study oligomerization of membrane proteins and peptides in nanodiscs with native mass spectrometry.Methods (San Diego, Calif.) · 2023Review
- Rapid Determination of the Topology of Oligomeric α-Helical Membrane Proteins by Water- and Lipid-Edited Methyl NMR.The journal of physical chemistry. B · 2023Article
- Differences in Oligomerization of the SARS-CoV-2 Envelope Protein, Poliovirus VP4, and HIV Vpu.bioRxiv : the preprint server for biology · 2023Article
- Association of COVID-19 with Comorbidities: An Update.ACS pharmacology & translational science · 2023Review
- In vitro anti-influenza assessment of anionic compounds ascorbate, acetate and citrate.Virology journal · 2022Article
- Potential antiviral effects of some native Iranian medicinal plants extracts and fractions against influenza A virus.BMC complementary medicine and therapies · 2021Article
- Virus Structures and Dynamics by Magic-Angle Spinning NMR.Annual review of virology · 2021Review
- Effects of an HIV-1 maturation inhibitor on the structure and dynamics of CA-SP1 junction helices in virus-like particles.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- M2 amphipathic helices facilitate pH-dependent conformational transition in influenza A virus.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Imidazole-Imidazole Hydrogen Bonding in the pH-Sensing Histidine Side Chains of Influenza A M2.Journal of the American Chemical Society · 2020Article
- The L46P mutant confers a novel allosteric mechanism of resistance toward the influenza A virus M2 S31N proton channel blockers.Molecular pharmacology · 2019Article
- The Transmembrane Conformation of the Influenza B Virus M2 Protein in Lipid Bilayers.Scientific reports · 2019Article
- South African medicinal plant extracts active against influenza A virus.BMC complementary and alternative medicine · 2018Article
17 more citing papers are in PubMed but not listed here.
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
The M2 protein of influenza A virus forms a transmembrane proton channel important for viral infection and replication. Amantadine blocks this channel, thus inhibiting viral replication. Elucidating the high-resolution structure of the M2 protein and its change upon amantadine binding is crucial for designing antiviral drugs to combat the growing resistance of influenza A viruses against amantadine. We used magic-angle-spinning solid-state NMR to determine the conformation and dynamics of the transmembrane domain of the protein M2TMP in the apo- and amantadine-bound states in lipid bilayers. (13)C chemical shifts and torsion angles of the protein in 1,2-dilauroyl-sn-glycero-3-phosphatidylcholine (DLPC) bilayers indicate that M2TMP is alpha-helical in both states, but the average conformation differs subtly, especially at the G34-I35 linkage and V27 side chain. In the liquid-crystalline membrane, the complexed M2TMP shows dramatically narrower lines than the apo peptide. Analysis of the homogeneous and inhomogeneous line widths indicates that the apo-M2TMP undergoes significant microsecond-time scale motion, and amantadine binding alters the motional rates, causing line-narrowing. Amantadine also reduces the conformational heterogeneity of specific residues, including the G34/I35 pair and several side chains. Finally, amantadine causes the helical segment N-terminal to G34 to increase its tilt angle by 3 degrees , and the G34-I35 torsion angles cause a kink of 5 degrees in the amantadine-bound helix. These data indicate that amantadine affects the M2 proton channel mainly by changing the distribution and exchange rates among multiple low-energy conformations and only subtly alters the average conformation and orientation. Amantadine-resistant mutations thus may arise from binding-incompetent changes in the conformational equilibrium.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.