Bacterial multidrug resistance (MDR) is a growing health problem that is a major challenge in the treatment of most infectious diseases. MDR is caused by the up-regulation of MDR efflux pumps that are imbedded in the cell membranes of bacteria. An important class of MDR pumps is the Multi Antimicrobial Toxin Extrusion (MATE) transporters from the Multidrug/Oligosaccharidyl-lipid/Polysaccharide (MOP) Super Family. MATE transporters translocate various hydrophobic substrates, such as norfloxacin by coupling them to either Na+ or H+ gradients. Our goal is ascertain the structural components that are involved in the translocation of drug molecules through the lipid bilayer by MATE transporters and to understand how these efflux pumps achieve their wide range of drug specificities. An important long-term objective is to provide a detailed structural framework for comprehending the general transport mechanisms that confer the MDR phenotype. A high-resolution atomic structure of a bacterial MATE transporter will also serve as an excellent model for other important secondary transporters that are involved in the translocation of sugars, amino acids, and ions. An x-ray structure of bacterial MATE transporters will also provide a structural basis for the translocation of substrate by homologous mammalian MOP transporters. ? ?
| He, Xiao; Szewczyk, Paul; Karyakin, Andrey et al. (2010) Structure of a cation-bound multidrug and toxic compound extrusion transporter. Nature 467:991-4 |
