Researchers at Carolina and GlaxoSmithKline have determined the structure of a molecule in the body responsible for regulating the metabolism of 60 percent of drugs taken by humans. The finding is another reminder that you need to be careful when mixing drugs with other drugs or even herbal supplements.

When taking oral contraceptives and St. John’s Wort at the same time, for instance, many women have unexpectedly gotten pregnant. Researchers knew that certain components in drugs and herbal supplements bind to a specific molecule in the liver, known as PXR, which turns on a protein that breaks down compounds in the liver, including contraceptives, making them ineffective.

Matthew R. Redinbo, assistant professor of chemistry, explains that PXR binds to different compounds depending on where the PXR came from. That means that in humans PXR binds to compounds that threaten humans, and in mouse models, PXR binds to a different set of chemicals that threaten mice. “But by changing only four amino acids in mouse PXR to the corresponding residues in human PXR,” Redinbo says, “we are able to humanize the mouse PXR receptor in its response to specific chemicals.”

That’s good news for humans because knowing the PXR crystal structure will allow scientists to identify and prevent more dangerous interactions between drugs.



Catherine House was formerly a staff contributor for Endeavors.