Protein Structure Offers Clues to Drug-Resistance Mechanism; New Study Sheds Light on How a Protein Pumps Toxic Molecules Out of Bacterial Cells

MIT chemists and colleagues have discovered the structure of a protein that can pump toxic molecules out of bacterial cells. Proteins similar to this one, which is found in E. coli, are believed to help bacteria become resistant to multiple antibiotics. Using nuclear magnetic resonance (NMR) spectroscopy, the researchers were able to determine how the structure of this protein changes as a drug-like molecule moves through it. Knowledge of this detailed structure may make it possible to design drugs that could block these transport proteins and help re-sensitize drug-resistant bacteria to existing antibiotics, says Mei Hong, PhD, an MIT professor of chemistry. “Knowing the structure of the drug-binding pocket of this protein, one might try to design competitors to these substrates, so that you could block the binding site and prevent the protein from removing antibiotics from the cell,” says Dr. Hong, who is the senior author of the paper.

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