title: Magic-angle-spinning NMR of the drug resistant S31N M2 proton transporter from influenza A.
abstract: We report chemical shift assignments of the drug-resistant S31N mutant of M2(18-60) determined using 3D magic-angle-spinning (MAS) NMR spectra acquired with a (15)N-(13)C ZF-TEDOR transfer followed by (13)C-(13)C mixing by RFDR. The MAS spectra reveal two sets of resonances, indicating that the tetramer assembles as a dimer of dimers, similar to the wild-type channel. Helicies from the two sets of chemical shifts are shown to be in close proximity at residue H37, and the assignments reveal a difference in the helix torsion angles, as predicted by TALOS+, for the key resistance residue N31. In contrast to wild-type M2(18-60), chemical shift changes are minimal upon addition of the inhibitor rimantadine, suggesting that the drug does not bind to S31N M2.
authors.affiliation: Francis Bitter Magnet Laboratory and Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
authors.forename: Loren B
authors.initials: LB
authors.lastname: Andreas
authors.forename: Matthew T
authors.initials: MT
authors.lastname: Eddy
authors.forename: James J
authors.initials: JJ
authors.lastname: Chou
authors.forename: Robert G
authors.initials: RG
authors.lastname: Griffin
mesh_terms: D000595:Amino Acid Sequence; D000998:Antiviral Agents / Q000494:pharmacology; D002352:Carrier Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000235:genetics; D024882:Drug Resistance, Viral; D006801:Humans; D009980:Influenza A virus / Q000737:chemistry* / Q000187:drug effects / Q000235:genetics; D007251:Influenza, Human / Q000188:drug therapy / Q000821:virology; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008969:Molecular Sequence Data; D009154:Mutation; D011522:Protons; D012299:Rimantadine / Q000494:pharmacology; D014764:Viral Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000235:genetics
chemical_list: D000998:Antiviral Agents; D002352:Carrier Proteins; D011522:Protons; D014764:Viral Proteins; D012299:Rimantadine