Japanese researchers have determined the detailed molecular structure of a protein that rids cells of toxins, but can also reduce the effectiveness of some antibiotics and cancer drugs by kicking them out of the cells they are targeting.
The scientists have also identified a molecule that can thwart the activity of the protein, one of a class known as multidrug and toxic compound extrusion transporters (MATEs) that are found in cell membranes. The discovery suggests new approaches to combat antibiotic resistance and boost the power of cancer therapies, the team reports today in Nature.
Previous efforts to identify compounds that block MATE transporters have been unsuccessful, partly because researchers had a poor understanding of how these proteins work. But in the past three years scientists have made some progress mapping the transporters’ detailed architecture. Two different labs have already revealed the structures of two bacterial MATE proteins, suggesting a mechanism by which the proteins extrude toxins from cells.
“I think this is a major step forward,” says Hendrik Van Veen, a pharmacologist at the University of Cambridge, UK. “They have a direct mechanism of how the protons change the shape of the cavity.”