Potentiation of the cystic fibrosis transmembrane conductance regulator by VX-770 involves stabilization of the pre-hydrolytic, O1 state.
Emily LangronStella PrinsPaola VerganiPublished in: British journal of pharmacology (2018)
Similar potentiation of hydrolytic and non-hydrolytic mutants suggests that VX-770 increases CFTR open probability mainly by stabilizing pre-hydrolytic O1 states with respect to closed states. Potentiation of K464A-CFTR channels suggests action of VX-770 did not strongly alter conformational dynamics at site 1. Understanding potentiator mechanism could help develop improved treatment for CF patients. The fluorescence assay presented here is a robust tool for such investigations.
Keyphrases
- cystic fibrosis
- pseudomonas aeruginosa
- end stage renal disease
- lung function
- ejection fraction
- newly diagnosed
- chronic kidney disease
- peritoneal dialysis
- high throughput
- molecular dynamics
- molecular dynamics simulations
- minimally invasive
- patient reported outcomes
- air pollution
- chronic obstructive pulmonary disease
- replacement therapy
- combination therapy