The main research focus of the Yu lab is to determine the structure, assembly and substrate transport mechanisms of the resistance-nodulation-cell division (RND)-superfamily of efflux pumps. These pumps are located within the inner membrane of Gram-negative bacteria and often assemble with other proteins (a soluble adapter protein and an outer membrane-spanning channel) to extrude harmful biocides out from the cell. This export process greatly enhances their viability and often the root cause of antibiotic resistant strains that are difficult to treat. Our main goal is to use X-ray crystallography/cryo-electron microscopy and other biophysical/biochemical techniques to solve the structures of these inner membrane efflux pumps, both alone and in conjunction with a variety of inhibitory compounds. Recent examples of inner membrane pump structures solved in our lab include HpnN from B. multivorans, MtrD from N. gonorrhoeae and MmpL3 from M. smegmatis. This structural information, combined with molecular docking studies, provides the foundation for the identification and development of new, potent molecules to help treat bacterial infections that are unable to be cured with the current available antibiotics.
PI: Edward Yu, Ph.D.