Magic-Angle-Spinning NMR of the Drug Resistant S31N M2 Proton Transporter from Influenza A

作者:Andreas Loren B; Eddy Matthew T; Chou James J; Griffin Robert G*
来源:Journal of the American Chemical Society, 2012, 134(17): 7215-7218.
DOI:10.1021/ja3003606

摘要

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 N-15-C-13 ZF-TEDOR transfer followed by C-13-C-13 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.

  • 出版日期2012-5-2