Research laboratory of William DeGrado, PhD

Thomaston solves drug-resistant M2-mutant crystal structure, published in Protein Science

Graduate student Jessica Thomaston recently had a paper accepted to Protein Science following up her work published in PNAS in 2015. Both use high resolution X-ray crystallography to investigate the role of water networks in proton transport and drug resistance in the M2 protein channel.

The M2 protein is a proton channel found in the influenza virus that is the target of two anti-influenza drugs. In recent decades drug-resistant mutants of the M2 channel have become prevalent, with the most common mutant being S31N. In this paper, we solved the first crystal structure of the M2 S31N mutant. We observe that the asparagines at position 31 point into the channel and prevent adamantane drugs from binding