title: Backbone structure of the amantadine-blocked trans-membrane domain M2 proton channel from Influenza A virus.
abstract: Amantadine is known to block the M2 proton channel of the Influenza A virus. Here, we present a structure of the M2 trans-membrane domain blocked with amantadine, built using orientational constraints obtained from solid-state NMR polarization-inversion-spin-exchange-at-the-magic-angle experiments. The data indicates a kink in the monomer between two helical fragments having 20 degrees and 31 degrees tilt angles with respect to the membrane normal. This monomer structure is then used to construct a plausible model of the tetrameric amantadine-blocked M2 trans-membrane channel. The influence of amantadine binding through comparative cross polarization magic-angle spinning spectra was also observed. In addition, spectra are shown of the amantadine-resistant mutant, S31N, in the presence and absence of amantadine.
authors: The National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA.
authors: Jun
authors: J
authors: Hu
authors: Tom
authors: T
authors: Asbury
authors: Srisairam
authors: S
authors: Achuthan
authors: Conggang
authors: C
authors: Li
authors: Richard
authors: R
authors: Bertram
authors: Jack R
authors: JR
authors: Quine
authors: Riqiang
authors: R
authors: Fu
authors: Timothy A
authors: TA
authors: Cross
mesh_terms: D000547:Amantadine / Q000737:chemistry*; D002462:Cell Membrane / Q000737:chemistry*; D003198:Computer Simulation; D015640:Ion Channel Gating; D009682:Magnetic Resonance Spectroscopy; D008956:Models, Chemical; D008958:Models, Molecular; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D014763:Viral Matrix Proteins / Q000737:chemistry* / Q000648:ultrastructure*; D000086082:Viroporin Proteins
chemical_list: D000547:Amantadine; D014763:Viral Matrix Proteins; C488937:M2 protein, Influenza A virus; D000086082:Viroporin Proteins