This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Our long-term goal is to elucidate the structures and fundamental mechanisms that give rise to drug recognition and extrusion in multidrug transporters. Recently, we have crystallized several AcrB mutants. Studying on these mutants is thought to be important for uncovering the mechanism of proton translocation in the pump. We will determine their x- ray structures with different ligands. AcrB exists as a complex with a membrane fusion protein, AcrA. To understand the mechanism of multidrug transport, the x-ray structure of the AcrAB complex is essential. We have co-crystallized the AcrAB efflux complex. The structure will provide us direct information about the mechanism of drug extrusion.
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