Neutron diffraction reveals the site of amantadine blockade in the influenza A M2 ion channel

Virology. 1994 Jul;202(1):287-93. doi: 10.1006/viro.1994.1345.

Abstract

The influenza A M2 protein forms proton channels which are blocked by the anti-influenza drug amantadine. Using the technique of neutron diffraction with both deuterium-labeled amantadine and influenza A M2 peptides, this study has directly located the position of interaction between the drug and the transmembrane domain of M2. Amantadine is found 0.5 nm from the center of the bilayer in an area between Val 27 and Ser 31, a location consistent with the formation of a steric block within the ion channel. Similar experiments with amantadine and an amantadine-resistant mutant peptide showed no such interaction.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Amantadine / pharmacology*
  • Amino Acid Sequence
  • Influenza A virus / drug effects*
  • Influenza A virus / ultrastructure
  • Ion Channels / antagonists & inhibitors*
  • Ion Channels / drug effects
  • Molecular Sequence Data
  • Neutrons
  • Phosphatidylcholines / chemistry
  • Viral Matrix Proteins / antagonists & inhibitors*
  • Viral Matrix Proteins / drug effects

Substances

  • Ion Channels
  • M-protein, influenza virus
  • M2 protein, Influenza A virus
  • Phosphatidylcholines
  • Viral Matrix Proteins
  • Amantadine
  • 1,2-oleoylphosphatidylcholine