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Protein Sci. 2016 Aug;25(8):1551-4. doi: 10.1002/pro.2937. Epub 2016 May 17.

Crystal structure of the drug-resistant S31N influenza M2 proton channel.

Author information

1
Department of Pharmaceutical Chemistry, University of California San Francisco, 555 Mission Bay Blvd. (S) Room 452V, San Francisco, California, 94158.

Abstract

The M2 protein is a small proton channel found in the influenza A virus that is necessary for viral replication. The M2 channel is the target of a class of drugs called the adamantanes, which block the channel pore and prevent the virus from replicating. In recent decades mutations have arisen in M2 that prevent the adamantanes from binding to the channel pore, with the most prevalent of these mutations being S31N. Here we report the first crystal structure of the S31N mutant crystallized using lipidic cubic phase crystallization techniques and solved to 1.59 Å resolution. The Asn31 residues point directly into the center of the channel pore and form a hydrogen-bonded network that disrupts the drug-binding site. Ordered waters in the channel pore form a continuous hydrogen bonding network from Gly34 to His37.

KEYWORDS:

S31N; crystal structure; influenza M2; proton channel

PMID:
27082171
PMCID:
PMC4972211
DOI:
10.1002/pro.2937
[Indexed for MEDLINE]
Free PMC Article

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