4.6 Article

An in-depth analysis of the biological functional studies based on the NMR M2 channel structure of influenza A virus

Journal

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
Volume 377, Issue 4, Pages 1243-1247

Publisher

ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2008.10.148

Keywords

Membrane protein channel; Virus; Drug-resistance; Rimantadine; Molecular wedge; Allosteric inhibition mechanism; Long-range interaction

Funding

  1. National High-tech Research and Development Program ('863') of China [2006AA020103]

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The long-sought three-dimensional structure of the M2 proton channel of influenza A virus Was Successfully determined recently by the high-resolution NMR [JR Schnell, JJ. 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 oil 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 Cities for dealing with the drug-resistance problems and developing new effective drugs against H5N1 avian influenza Virus, all impending threat to human beings. (C) 2008 Elsevier Inc. All rights reserved.

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