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.

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Authors

Andreas LB, Eddy MT, Chou JJ, Griffin RG

Institution

Francis Bitter Magnet Laboratory and Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.

Source

Journal of the American Chemical Society 134:17 2012 May 2 pg 7215-8

MeSH

Amino Acid Sequence
Antiviral Agents
Carrier Proteins
Drug Resistance, Viral
Humans
Influenza A virus
Influenza, Human
Magnetic Resonance Spectroscopy
Molecular Sequence Data
Mutation
Protons
Rimantadine
Viral Proteins

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

22480220