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Bacterial protein recycling factor possible key to new class of antibiotics

(Philadelphia, PA) Understanding the last step of protein synthesis the basic process of translating DNA into its final protein product just became more clear both literally and figuratively. This final phase, called recycling, is essential for the proper function of all cells. Using a three-dimensional cryo-electron microscope to directly observe protein structure, investigators at the University of Pennsylvania School of Medicine and the State University of New York, Albany can now visualize the exact configuration of a molecule called ribosome recycling factor (RRF) in the common bacteria Escherichia coli. This image reported in the June 15 issue of the Proceedings of the National Academy of Sciences may help guide the design of new antibiotics aimed at inhibiting RRF-related steps of protein synthesis.

"Every living organism has to have this last step, the recycling of spent protein synthesis machinery for the next round of translation," says Akira Kaji, PhD, Professor of Microbiology at Penn. "Strangely, at this day and age, this most fundamental process remained vague until we launched our studies of RRF."

Most antibiotics influencing protein synthesis act by stopping its molecular machinery. However, none as yet target the recycling step. "We believe RRF is one of the best candidates for a new antibiotics target because the mechanism involved in recycling of the protein-making machinery is different in eukaryotes versus prokaryotes, that is humans versus bacteria," says Kaji. "With the emergence of antibiotic-resistant pathogens, this will be the best avenue of devising new antibiotics."

Thirty Years of Searching

The ribosome is the structure within cells on which amino acids are strung together to make proteins with the aid of transfer RNA (tRNA) and messenger RNA (mRNA). Kaji has spent the past 30 years working out the last step of protein synthesis. RRF, in conjunction with elongation factor G (EF-G), moves alo
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Contact: Karen Kreeger
karen.kreeger@uphs.upenn.edu
215-349-5658
University of Pennsylvania School of Medicine
30-Jun-2004


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