Neutron diffraction reveals the site of amantadine blockade in the influenza A M2 ion channel.
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.
Duff
K C
KC
Department of Biochemistry, University of Edinburgh Medical School, United Kingdom.
Gilchrist
P J
PJ
Saxena
A M
AM
Bradshaw
J P
JP
D000547:Amantadine / Q000494:pharmacology*; D000595:Amino Acid Sequence; D009980:Influenza A virus / Q000187:drug effects* / Q000648:ultrastructure; D007473:Ion Channels / Q000037:antagonists & inhibitors* / Q000187:drug effects; D008969:Molecular Sequence Data; D009502:Neutrons; D010713:Phosphatidylcholines / Q000737:chemistry; D014763:Viral Matrix Proteins / Q000037:antagonists & inhibitors* / Q000187:drug effects; D000086082:Viroporin Proteins
D000547:Amantadine; D007473:Ion Channels; D010713:Phosphatidylcholines; D014763:Viral Matrix Proteins; C031540:M-protein, influenza virus; C488937:M2 protein, Influenza A virus; D000086082:Viroporin Proteins; C017251:1,2-oleoylphosphatidylcholine