Mechanism of drug inhibition and drug resistance of influenza A M2 channel.

ABSTRACT: The influenza A virus M2 proton channel equilibrates pH across the viral membrane during entry and across the trans-Golgi membrane of infected cells during viral maturation. It is an important target of adamantane-family antiviral drugs, but drug resistance has become a critical problem. Two different sites for drug interaction have been proposed. One is a lipid-facing pocket between 2 adjacent transmembrane helices (around Asp-44), at which the drug binds and inhibits proton conductance allosterically. The other is inside the pore (around Ser-31), at which the drug directly blocks proton passage. Here, we describe structural and functional experiments on the mechanism of drug inhibition and resistance. The solution structure of the S31N drug-resistant mutant of M2, a mutant of the highly

SUBMITTER: Pielak RM 

PROVIDER: S-EPMC2678642 | biostudies-literature | 2009 May

REPOSITORIES: biostudies-literature