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Scientists identify molecular structure of cancer-related proteins

NEW YORK, December 18, 2001 Research published in this weeks issue of Nature describes the molecular structure of two cancer-related proteins binding to one another. Scientists identified the biochemical and signaling properties of these molecules using a process called X-ray crystallography. The technique yielded the first-ever detailed pictures of the proteins interacting with each other, indicating which areas are most essential for the development of cancer.

The characterization of the structure may eventually be used to design novel drugs that interfere with the normal function of these proteins and prevent cancer growth. The work is the result of a scientific collaboration led by Memorial Sloan-Kettering Cancer Center. Tyrosine kinases are key enzymes responsible for communication between receptors on the cells surface and pathways within the cell. Researchers determined the structure of an Eph receptor tyrosine kinase bound to its corresponding ligand molecule called ephrin. Interactions between Eph receptors and their specific ephrins lead to an array of cellular processes, including those that regulate cell proliferation, survival, adhesion, and movement. They are especially important in angiogenesis the development of new blood vessels essential for the progression of cancer.

According to the authors, the structural detail of the complex provides a framework for the development of potential drugs that could block Eph signaling. Given the importance of Eph receptor kinases and ephrins in cardiovascular function, nerve regeneration, and cancer, the results could be the first step towards the future development of novel therapeutic strategies, said Dimitar Nikolov, PhD, head of the Structural Biology and Neuroscience Laboratory at Memorial Sloan-Kettering Cancer Center, and senior author of the study.

The research team cloned the Eph and ephrin mouse genes, expressed the corresponding proteins in bacteria, and then purified them
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Contact: Esther Carver
212- 639-3573
Memorial Sloan-Kettering Cancer Center
27-Dec-2001


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