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2 Americans, Israeli share Nobel Prize in chemistry

Two Americans and an Israeli who mapped the precise structure of the ribosome -- the cell's critical protein-making factory -- won the 2009 Nobel Prize in chemistry Wednesday.

Their independent work, published in 2000, provides fundamental information about the workings of cells at the atomic level and is already being exploited by drug companies working to make more effective antibiotics.

The $1.4-million prize will be shared equally by Thomas A. Steitz of Yale University; Venkatraman Ramakrishnan of the Medical Research Council Laboratory of Molecular Biology in Cambridge, England, an Indian-born U.S. citizen; and Ada E. Yonath of the Weizmann Institute of Science in Rehovot, Israel.

Yonath is the only one of this year's nine science winners who is not an American citizen, either native or naturalized. She is the first woman to win the chemistry Nobel since Dorothy Crowfoot Hodgkin of Britain received the 1964 prize. Yonath is also the first Israeli woman to win a Nobel.

The ribosome, which is made up of a large and small subunit, translates the cell's genetic information into the thousands of proteins that enable the cell to function: The proteins it produces carry out chemical reactions and provide the cell's structural foundation.

The three Nobelists used a technique called X-ray crystallography to determine the ribosome's structure. X-ray crystallography is a time-consuming, tedious science, requiring excruciating patience and care to produce crystals of cellular proteins and sophisticated math to analyze X-ray patterns that arise when an X-ray beam is focused on such crystals.

This is difficult with even small proteins, and many researchers thought it would be impossible with the ribosome, which is made of many different proteins and also contains pieces of RNA. Getting such a large, amorphous structure to form precise crystals had never been attempted before.

"When these researchers began their work, determining the structure and mechanism of the ribosome seemed nearly impossible," said Jeremy M. Berg, director of the National Institute of General Medical Sciences, which funded all three investigators.

Yonath began trying to grow crystals in the early 1970s, working with a bacterium that can grow under harsh conditions such as near-boiling water. Her assumption was that this microbe's ribosomes would be more stable and more resistant to degradation during the process of inducing crystal formation.

After 20 years, it finally became clear that she could produce such crystals, and other researchers such as Steitz and Ramakrishnan joined the race to complete the work.

But there still were daunting obstacles to overcome. The X-ray images produced directly from a crystal are insufficient to reveal its structure. They lack crucial mathematical information that researchers call phase angles. This information is typically obtained by seeding the crystals with heavy metal atoms, such as mercury. But ribosomes are so large that obtaining the phase angles was exceedingly difficult.

Steitz's contribution was to determine how the ribosomes were oriented within the crystal. That, combined with the information from heavy metals, finally made it possible to determine phase angles and, in 1998, Steitz published the first crude crystal structure of the ribosome's large subunit.

It was then necessary only to improve the crystals and obtain more data to increase the sharpness of the image, allowing researchers to locate every atom within the assemblage.

In 2000, Steitz published the refined structure of the large subunit and Yonath and Ramakrishnan each published that of the small subunit.

The work could prove invaluable in the search for new antibiotics to fight infections. At least half of all antibiotics work by blocking the activity of ribosomes in bacteria without affecting those in human cells. But bacteria have grown resistant to most of them. Using the new ribosome images, pharmaceutical companies have been able to determine how the antibiotics function and thus to design new molecules that circumvent resistance.

"Scientists around the world are using the winners' research to develop new antibiotics that can be used in the ongoing battle against antibiotic-resistant bacteria that cause so much illness, suffering and death," said Thomas H. Lane, president of the American Chemical Society.

Yonath, 70, was born in Jerusalem and trained at the Weizmann Institute of Science, where she has spent her entire career. "I'm really, really happy," she said of the award.

Steitz, 69, was born in Milwaukee and is a Howard Hughes Medical Institute researcher at Yale University. Solving the problem, he said, "was the most exhilarating moment I have had in science."

Ramakrishnan, 57, was born in Chidambaram, Tamil Nadu, India, and received his doctorate from Ohio University. He said he at first thought the early morning call from the Nobel Foundation was a joke being played by one of his friends. "I complimented him on his Swedish accent," he said.

thomas.maugh@latimes.com

Times staff writer Richard Boudreaux in Jerusalem contributed to this report.

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