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Yale researchers solve structure of the ribosome: groundbreaking achievement 'like climbing Mount Everest'

In a landmark achievement, Yale researchers have determined the atomic structure of the ribosome's large subunit, paving the way for more effective drugs to fight infection.

The findings, published in two separate articles in this week's issue of the journal Science, were derived in Yale laboratories led by Thomas Steitz, the Eugene Higgins Professor of Molecular Biophysics and Biochemistry and investigator at the Howard Hughes Medical Institute, and Peter Moore, the Eugene Higgins Professor of Chemistry.

"This is like climbing Mt. Everest or running the four minute mile," Steitz said. "We have solved the structure of the ribosome's large subunit, which is the largest unique structure determined. We have established that the ribosome is a ribozyme, an enzyme in which catalysis is done by RNA, not protein."

The ribosome is the cellular structure responsible for synthesizing protein molecules in all organisms. In addition to enhancing the understanding of protein synthesis, the research offers new clues about evolution and has significant medical implications because the ribosome is a major target for antibiotics.

Many antibiotics cure disease by selectively inhibiting the protein synthesizing activity of large ribosomal subunits in disease-causing bacteria, while leaving human ribosomes alone. Unfortunately, over the years, many bacteria have become resistant

to these agents, and the possibility exists that the devastating bacterial diseases that were brought under control by antibiotics in the 1940s and 1950s will once again become scourges.

"Now that we know the structure of the large ribosomal subunit," Steitz said, "we can determine its exact structure with antibiotics bound to it." The same methods of "structure-based drug design" that led to the development of HIV protease inhibitors for AIDS can now be used on the ribosome, which is 100 times larger.

"The information that emerges should enable pharmaceutical co
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Contact: Karen Peart
karen.peart@yale.edu
203-432-1326
Yale University
9-Aug-2000


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