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Fowler Lab
Fowler Lab

Predicting antibiotic resistance de novo

New Publication: State-Dependent Network Connectivity Determines Gating in a K+ Channel

Philip Fowler, 27th June 2014

In an earlier paper we showed that the closed state of Kir1.1, a important potassium ion channel found in the kidneys, was stabilised by a single hydrogen bond. This paper builds on that work by looking for any interactions that stabilise either the open or closed state of the channel by systematically mutating the majority of the residues to alanine. We were surprised to find that 47 mutations destabilised the open state but only 2 destabilised the closed state, one of which was the one we’d found before. Modelling suggests that this is because open conformations of the channel are more optimised and compact hence mutations tend to be more disruptive. The work was partly funded by the Wellcome Trust and hence the paper is free to download.

fig-k11-2

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