An in-depth analysis of the biological functional studies based on the NMR M2 channel structure of influenza A virus.
The long-sought three-dimensional structure of the M2 proton channel of influenza A virus was successfully determined recently by the high-resolution NMR [J.R. Schnell, J.J. Chou, Structure and mechanism of the M2 proton channel of influenza A virus, Nature 451 (2008) 591-595]. Such a milestone work has provided a solid structural basis for studying drug-resistance problems. However, the action mechanism revealed from the NMR structure is completely different from the traditional view and hence prone to be misinterpreted as "conflicting" with some previous biological functional studies. To clarify this kind of confusion, an in-depth analysis was performed for these functional studies, particularly for the mutations D44N, D44A and N44D on position 44, and the mutations on positions 27-38. The analyzed results have provided not only compelling evidences to further validate the NMR structure but also very useful clues for dealing with the drug-resistance problems and developing new effective drugs against H5N1 avian influenza virus, an impending threat to human beings.
Huang
Ri-Bo
RB
Guangxi Academy of Sciences, 98 Daling Road, Nanning, Guangxi 530004, China.
Du
Qi-Shi
QS
Wang
Cheng-Hua
CH
Chou
Kuo-Chen
KC
D000595:Amino Acid Sequence; D000998:Antiviral Agents / Q000494:pharmacology; D001224:Aspartic Acid / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D024882:Drug Resistance, Viral / Q000235:genetics; D009980:Influenza A virus / Q000187:drug effects / Q000378:metabolism; D015640:Ion Channel Gating; D008969:Molecular Sequence Data; D009154:Mutation; D019906:Nuclear Magnetic Resonance, Biomolecular; D017433:Protein Structure, Secondary; D014763:Viral Matrix Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D000086082:Viroporin Proteins
D000998:Antiviral Agents; D001224:Aspartic Acid; D014763:Viral Matrix Proteins; C488937:M2 protein, Influenza A virus; D000086082:Viroporin Proteins