2 Americans, Israeli share Nobel Prize in chemistry

They used X-ray crystallography to map the structure of a key cell
component, a breakthrough that pharmaceutical companies are now
using to make more effective antibiotics.

By Thomas H. Maugh II
Los Angeles Times
http://www.latimes.com

Two Americans and an Israeli who used X-ray crystallography to 
map the precise structure of the ribosome, the cell's crucial
protein-making factory, today won the 2009 Nobel Prize in 
chemistry.

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

The $1.4-million prize will be shared equally by Thomas A. Steitz
of Yale University; Venkatraman Ramakrishnan of the MRC Laboratory
of Molecular Biology in Cambridge, England, who was born in India
but is now a U.S. citizen; and Ada E. Yonath of the Weizmann
Institute of Science in Revovot, 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, and who was also
honored for her contributions to X-ray crystallography. Yonath is
also the first Israeli woman to win a Nobel.

"It's true that a woman hasn't won since 1964," she told Israeli
radio. "But I don't know what that means. Does it mean that I'm the
best woman since then? I don't think gender played a role here."
Her radio chat had to be cut short because of a call from Israeli
President Shimon Peres.

On Monday, Elizabeth Blackburn of UC San Francisco and Carol W.
Greider of Johns Hopkins University School of Medicine shared the
medicine Nobel with Jack W. Szostak of Harvard Medical School,
marking the first time that two women had won that prize in the
same year. The awards, experts said, mean that the many
contributions of women to science are finally beginning to be
recognized.

X-ray crystallography is a time-consuming and tedious science that
requires excruciating patience and care to produce crystals of
cellular proteins and then sophisticated mathematics to analyze the
X-ray patterns that arise when an X-ray beam is focused on such
crystals. This is a difficult process with small proteins from
cells, and many researchers thought it would be impossible with the
ribosome, which is one of the largest proteins in living organisms.

The ribosome translates the cell's genetic information into the
proteins that actually make the cell function. It has a large and 
a small subunit, each of which contains thousands of the
nucleotides that comprise RNA and thousands of the amino acids that
comprise proteins. Getting such a large, amorphous molecule to form
precise crystals was something that had never been attempted 
before.

Undaunted, Yonath began trying to grow crystals in the early 1970s,
working with a bacterium that can grow under harsh environmental
conditions on the assumption that its ribosomes would be more
stable and thus more resistant to degradation during the process of
inducing crystals to form.

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

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.

With that advance, 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 individual atom within
the assemblage.

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

Many 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 actually function and to design new molecules that will
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. 
She has also worked with NASA on 12 missions, sending biological
materials into space. Some of those were attempts to grow crystals
in microgravity. "I'm really, really happy," she said of the award.
"I thought it was wonderful when the discovery came. It was a
series of discoveries. . . . We still don't know everything, 
but we progressed a lot."

Steitz, 69, was born in Milwaukee and is a Howard Hughes Medical
Institute researcher at Yale.

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.