Energy-coupling factor transporters: exploration of the mechanism of vitamin uptake and inhibitory potential of novel binders

This thesis presents investigations of small molecule ligands that inhibit vitamin uptake by Energy Coupling Factor (ECF) transporters, which form a subclass of ATP-binding cassette (ABC) transporters. The long-term vision is that these molecules may lead to development of novel antibiotics with an unrivalled mechanism of action. In addition, I explored the mechanism how vitamins are translocated across a membrane bilayer via these transporters. For these goals, the ECF transporters from Lactococcus lactis and Lactobacillus delbrueckii specific for thiamin, folate and pantothenate were studied using biochemical, biophysical and structural biological techniques.