October 2001

From Weizmann Institute

Scientists uncover the exact mode of action of five antibiotic drugs

Rehovot, Israel—October 24, 2001—Researchers from the Weizmann Institute of Science and Germany’s Max-Planck Society have discovered how five antibiotic drugs function by binding to the bacterial ribosome – the cell’s "protein factory" – and shutting off all protein production. Proteins are the cells primary component and the basis of all enzymatic reactions. Blocking their production kills the bacterium.

The research team headed by Prof. Ada Yonath of the Weizmann Institute’s Structural Biology Department and the Max-Planck Research Units for Ribosomal Structure in Hamburg and Berlin uncovered the exact mode of action of these drugs. Prof. Yonath recently revealed the complex structure of the ribosome, culminating 20 years of scientific research in a study described by the prestigious journal Science, as one of the most important scientific discoveries of the year 2000. The goal of elucidating the structure of the ribosome – a notoriously unstable, giant nucleoprotein complex – had challenged scientists for years.

Using their extensive understanding of ribosomal structure, Prof. Ada Yonath, Dr. Anat Bashan and Ph.D. Student Raz Zarivach, decided to examine how different antibiotics bind to the ribosome and “shut off” its protein production. To do so they treated bacteria with one of five different antibiotics and then created crystals capturing the individual complexes formed between the bacterial ribosome and each drug.

To examine these microscopic structures, the scientists bombarded the crystals with high intensity X-ray beams, analyzed how the rays diffract, and then worked backward to decipher the crystal’s exact structure – a technology known as X-ray crystallography. Using this method, the researchers were able, for the first time, to view how the antibiotic drugs bind to a specific site of action on the ribosome, shutting off its machinery. These findings are reported today in Nature.

A better understanding of the mode of action of antibiotic drugs may improve the treatment strategies of existing drugs, and lead to rational drug design of antibiotics designed to better target bacterial agents at the ribosomal level.

The Max-Planck scientists collaborating in this study are Francois Franceschi, Joerg Harms, Ante Tocilj, Renate Albrecht, and Frank Schluenzen.

A hard copy color picture is available upon request. The image is also posted at: http://wis-wander.weizmann.ac.il/weizmann/doa_iis.dll/Serve/level/English/1.200.html

Donor support: The Helen & Milton A. Kimmelman Center for Biomolecular Structure & Assembly, the Joseph and Ceil Mazer Foundation, and the Solomon and Rebecca Baker Foundation. Professor Ada Yonath is the incumbent of the Martin S. Kimmel Professorial Chair.

The Weizmann Institute of Science, in Rehovot, Israel, is one of the world’s foremost centers of scientific research and graduate study. Its 2,500 scientists, students, technicians and engineers pursue basic research in the quest for knowledge and to enhance the quality of human life. New ways of fighting disease and hunger, protecting the environment and harnessing alternative sources of energy are high priorities at Weizmann.












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