Premium
Crystal structure of the drug‐resistant S31N influenza M2 proton channel
Author(s) -
Thomaston Jessica L.,
DeGrado William F.
Publication year - 2016
Publication title -
protein science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.353
H-Index - 175
eISSN - 1469-896X
pISSN - 0961-8368
DOI - 10.1002/pro.2937
Subject(s) - channel (broadcasting) , point mutation , mutant , crystallization , chemistry , crystallography , gene , biochemistry , engineering , organic chemistry , electrical engineering
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.