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HWI scientist first in world to unravel structure of key breast cancer target enzyme
Date:1/7/2009

The molecular details of Aromatase, the key enzyme required for the body to make estrogen, are no longer a mystery thanks to the structural biology work done by the Ghosh lab at the Hauptman-Woodward Medical Research Institute (HWI) in Buffalo, New York. Dr. Debashis Ghosh's solution of the three-dimensional structure of aromatase is the first time that scientists have been able to visualize the mechanism of synthesizing estrogen.

In fact, the Ghosh lab has determined the structures of all three of the enzymes involved in controlling estrogen levels that can serve as drug targets for estrogen-dependent tumors in breast cancer. This work is so significant, the world-renowned journal Nature will be publishing the structure of aromatase at 2.90 angstrom resolution in an upcoming issue. The other two enzyme structures determined by the Ghosh lab as part of this project were estrone sulfatase (2003) and 17beta-hydroxysteroid dehydrogenase type 1 (1996). All three enzymes control the levels of estradiol in different tissues.

"This is a dream come true," Dr. Debashis Ghosh, an HWI senior research scientist and a principal investigator who also holds a joint faculty appointment at the Roswell Park Cancer Institute (RPCI), said. "Scientists worldwide have been trying for 35 years to crystallize this membrane-bound enzyme and we are the first to succeed. Now that we know the structures of all three key enzymes implicated in estrogen-dependant breast cancers, our goal is to have a personalized cocktail of inhibitors customized to the specific treatment needs of each patient. Our knowledge about these three enzymes will enable us to develop three mutually exclusive inhibitors customized to each patient's needs which will work in harmony together with minimal side effects."

Why Is This Important?

Most people know that breast cancer is the most common cancer among women in the United States and the second leading cause o
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Contact: Tara A. Ellis
tellis@hwi.buffalo.edu
716-898-8596
Hauptman-Woodward Medical Research Institute
Source:Eurekalert  

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