Structural insights into protein-ligand-membrane interactions of the bacterial membrane protein MraY: synthesis and application of chemical probes
The overall goal of the described project will be to obtain molecular insights into inhibition of the bacterial membrane protein MraY. Analogues of naturally occurring MraY inhibitors will be synthesized via a modular synthetic route. These chemical probes will be tested for their MraY inhibitor potency under different conditions. Fluorescent MraY binders will be prepared and will enable biophysical investigations on MraY-containing membrane model systems. Potential conformational changes of MraY upon inhibitor and/or cosubstrate binding will be studied using NMR and X-ray techniques.