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Structure solved at Scripps shows how one human protein reduces potency of chemotherapy

A team of researchers led by scientists at The Skaggs Institute for Chemical Biology at The Scripps Research Institute have solved the structure of a human protein called AGT that is known to interfere with the action of certain chemotherapy drugs.

AGT repairs damaged DNA inside human cells. Cancer cells can use it to repair DNA that has been damaged in the course of chemotherapythus rendering the chemotherapy ineffective.

The structure of AGT, which is being reported in an upcoming issue of the journal Nature Structural & Molecular Biology, was solved in the laboratory of Scripps Research Professor John Tainer, Ph.D., by Research Associate Douglas Daniels, Ph.D. The fine details of this x-ray structure may help scientists find ways to fight certain cancers, such as brain tumors, which express high levels of AGT making them resistant to chemotherapy.

"This structure provides a solid foundation for the development of better drugs and resistant proteins [intended to improve cancer therapies]," says Tainer.

Cancer, Chemotherapy, and Resistance

Cancer is one of the greatest public health scourges in the United States today. According to the U.S. Centers for Disease Control and Prevention, it is the second leading cause of death. In 2001, the most recent year for which such statistics are available, 553,768 people died of some form of cancer.

For years, one of the best available ways to treat cancer has been through the administration of chemotherapy drugs, such as "alkylating" agents, which inhibit the growth of cancer cells by damaging their DNA.

DNA, the molecule that stores our genetic information, is composed of two intertwining helical strands that bind to each other through base pairing. Each strand is composed of four types of DNA bases (A, G, C, and T) attached to one another through a sugar-phosphate backbone. The other strand in the pair has a complementary sequence of bases.

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Contact: Jason Bardi
jasonb@scripps.edu
858-784-9254
Scripps Research Institute
7-Jul-2004


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