June 18, 2001

1 min read

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Scientists Discover Structure of Molecule That Metabolizes Most Drugs

By Kate Wong

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Scientists have discovered the structure of a molecule responsible for metabolizing more than half of all drugs, according to the results of a new study. The findings, published online by the journal Science, will help drug manufacturers to better understand how drugs are broken down and disposed of, and should aid in preventing dangerous cross-reactions between drugs.

This key molecule, dubbed PXR, controls a protein known as cytochrome P450-3A (abbreviated to CYP3A) that breaks down medications. It does this by binding to the compounds, thereby tagging them for degradation. But in contrast to most biological interactions, in which a molecule or receptor binds to a single chemical, University of North Carolina chemist Matthew R. Redinbo notes, PXR is "highly promiscuous," binding to compounds ranging from the anti-cancer drug Taxol to the abortion pill RU-486. If someone is taking more than one drug, this can lead to problems. "Imagine you are taking oral contraceptives and at the same time the herb St. John's wort," Redinbo says. "It's known that a constituent of St. John's wort, hyperforin, binds to PXR and turns on CYP3A4, which then breaks down lots of compounds in the liver, including contraceptives." Other negative interactions mediated by PXR, he adds, can lead to breakdown of the immunosuppressant cyclosporin and the anti-HIV drug Indinavir. The new work provides welcome insight into the mediating molecule. "Using the crystal structure of PXR," Redinbo remarks, "we may be able to predict these effects and prevent such drug-drug interactions."

Kate Wong is an award-winning science writer and senior editor for features at Scientific American, where she has focused on evolution, ecology, anthropology, archaeology, paleontology and animal behavior. She is fascinated by human origins, which she has covered for nearly 30 years. Recently she has become obsessed with birds. Her reporting has taken her to caves in France and Croatia that Neandertals once called home to the shores of Kenya’s Lake Turkana in search of the oldest stone tools in the world, as well as to Madagascar on an expedition to unearth ancient mammals and dinosaurs, the icy waters of Antarctica, where humpback whales feast on krill, and a “Big Day” race around the state of Connecticut to find as many bird species as possible in 24 hours. Wong is co-author, with Donald Johanson, of Lucy’s Legacy: The Quest for Human Origins. She holds a bachelor of science degree in biological anthropology and zoology from the University of Michigan. Follow her on Bluesky @katewong.bsky.social

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