Community Research and Development Information Service - CORDIS



Project ID: 282083
Funded under: FP7-IDEAS-ERC
Country: Netherlands

Final Report Summary - ABCTRANSPORT (Minimalist multipurpose ATP-binding cassette transporters)

Many pathogenic bacteria are dependent on the uptake of vitamins from the environment or from the infected host. The long-elusive protein complexes that mediate such uptake were recently discovered. The uptake proteins could turn out to be an Achilles’ heel for the bacteria and therefore may be targets for new antibacterial drugs. To establish whether drugs can indeed target them, it is
indispensable to obtain basic insight in the workings of the proteins, which will allow the rational design of “spanners in the works”.

Our work has revealed the three-dimensional structure of the transport proteins, which is essential to design inhibiting molecules. We also have established assays to study the function and dynamics of the proteins, which is essential to test whether the small molecules are effective. We have proposed a mechanistic model for the workings of the molecular motor of the vitamin transport protein s that differs from any known transport mechanism. Using this model we have designed, synthesized and tested the first small molecules that inhibit vitamin uptake. This work provides a strong basis for further development of potential antibacterial drugs.

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