Structure and function of membrane transporters (Edward Yu)
We currently focus on the structural basis of multi-drug resistance in multi-drug membrane transporters. Multi-drug transporters interfere significantly with cancer chemotherapy and the treatment of bacterial infections, by recognizing a number of structurally unrelated toxic compounds and actively extruding them from cells. Our long-term goal is to elucidate the structures and fundamental mechanisms that give rise to multiple drug recognition and extrusion in these multi-drug transporters. Using X-ray crystallography and site-directed mutagenesis, we study the structural and functional relationship of the Escherichia oli AcrB transmembrane efflux pump, which shows the widest substrate specificity among all known multi-drug transporters, ranging from most of the currently used antibiotics, disinfectants, dyes, detergents, to simple solvents. This information is expected to help in the redesign of old drugs and the development of new drugs as well as combinations of two or more drugs for greater effect.