Kurt Wüthrich of The Scripps Research Institute
Wins 2002 Nobel Prize in Chemistry
Second Nobel Prize in a Row for TSRI
Kurt Wüthrich, Ph.D., who is Cecil H. and Ida M. Green
Visiting Professor of Structural Biology at The Scripps Research
Institute (TSRI) and a member of TSRI's Skaggs Institute for
Chemical Biology; and Professor of Biophysics at Eidgenössische
Technische Hochschule Zürich (ETHZ), Switzerland, was
awarded the 2002 Nobel Prize in Chemistry today for applying
the technique of nuclear magnetic resonance (NMR) to solving
the structures of biological macromolecules.
Biological macromolecules—the DNA, proteins, sugars,
and lipids of life—make up all the important structures
of the cell, but they are much too small to study under a
microscope. Determining the structure of these macromolecules
through NMR was pioneered by Wüthrich and allows scientists
to "see" what they look like, to study and probe their structures,
and to design drugs that inhibit them. Most recently, NMR
structures have been critical in the design of drugs to treat,
for instance, cancer and HIV.
"We are thrilled that Dr. Wüthrich has received this
recognition," says TSRI President Richard Lerner, M.D. "He
is in the forefront of his field and he continues to push
the boundaries of structural biology in new and important
ways."
Awarded annually by the Royal Swedish Academy of Sciences
for achievements in physics, chemistry, medicine, literature,
economics, and peace, the prize recognizes individuals who,
as stipulated in Alfred Nobel's will, "have conferred the
greatest benefit on mankind." Each prize carries a cash award
of roughly one million dollars. Last year, K. Barry Sharpless,
Ph.D., W.M. Keck Professor of Chemistry at TSRI and member
of TSRI's Skaggs Institute for Chemical Biology, was awarded
the 2001 Nobel Prize in Chemistry for the development of catalytic
asymmetric synthesis.
"Two Nobel Prizes in two years is a remarkable endorsement
of what TSRI is about—attracting the very best scientific
minds and providing them the resources and freedom they need
to produce the very best research," Lerner says. "The prizes
also underscore the extraordinary quality of the TSRI structural
biology and chemistry programs."
Wüthrich, who currently operates a laboratory at TSRI
and is scheduled to become a full-time faculty member in 2004,
was awarded half this year's prize in chemistry specifically
"for his development of nuclear magnetic resonance spectroscopy
for determining the three-dimensional structure of biological
macromolecules in solution," according to the Nobel web site.
John B. Fenn of the Virginia Commonwealth University in the
United States and Koichi Tanaka of the Shimadzu Corporation
in Japan share the other half "for their development of soft
desorption ionisation methods for mass spectrometric analyses
of biological macromolecules."
In 1982, Wüthrich's group published a series of four
papers that outlined a framework for NMR structure determination
of proteins. In 1984, he published the first protein structure
determined by NMR—that of the protein bull seminal protease
inhibitor. He is author of the definitive book on the subject,
"NMR of Proteins and Nucleic Acids" (1986).
In addition to developing methodology, Wüthrich has
devoted his research to solving structures of biological molecules.
He has solved more than 50 novel NMR structures of proteins
and nucleic acids, including the immunosuppression system
cyclophilin A–cyclosporin A, the homeodomain operator
DNA transcriptional regulation system, and the murine, human,
and bovine prion proteins. Misfolded prion proteins are believed
to be the cause of bovine spongiform encephalopathy, or mad
cow disease, and a form of the disease in humans, called variant
Creutzfeldt-Jakob Disease.
Wüthrich has solved numerous protein pheromone structures
from Mediterranean sea creatures and pheromone-binding proteins
from other organisms, such as silkworms. He is also looking
at "chaperonin" systems like GroEL—the very large protein
complex that monitors the folding of newly synthesized proteins.
He also has been looking at ways of solving membrane protein
structures, which are some of the least solved of all the
relevant molecular structures in biology. Less than one half
of one percent of the structures contained in the Brookhaven
National Laboratory Protein Data Bank are of integral membrane
proteins, despite the fact that over a third of all proteins
in the body are in the membrane.
Most recently, Wüthrich pioneered the new technique
of transverse relaxation-optimized spectroscopy NMR (TROSY),
which extends several-fold the size limit of structures that
can be solved with NMR. This made it possible for the first
time for investigators to use NMR to solve many important
biological structures—such as large proteins and protein/protein,
protein/DNA or protein/lipid complexes—that are impossible
to investigate with conventional NMR, which cannot solve structures
larger than 50,000 daltons. A dalton is equivalent to the
mass of one hydrogen atom.
"We can now do reasonably detailed structural investigations
of proteins in structures of size up to about 150,000 daltons,"
says Wüthrich.
He has also pioneered other techniques, such as cross-correlated
relaxation-enhanced polarization transfer (CRINEPT), which
when combined with TROSY, result in highly effective experiments
for very large structures. "We can go up to one million [daltons],
essentially," Wüthrich says.
Wüthrich did his undergraduate training at the University
of Bern, Switzerland, receiving a Licentiat in chemistry,
physics and mathematics in 1962. In 1964, he was awarded a
Ph.D. in chemistry from the University of Basel, Switzerland,
(studying with Professor S. Fallab), where he also completed
a year of postdoctoral training. After an additional two years
of postdoctoral training at the University of California,
Berkeley, Wüthrich worked for two years as a member of
the technical staff at Bell Telephone Laboratories in Murray
Hill, New Jersey. In 1969, he moved to the Eidgenössische
Technische Hochschule Zürich (ETHZ), Switzerland, where
he is currently Professor of Biophysics.
Wüthrich is a Member of the European Molecular Biology
Organization; a Member of the Academia Europaea; a Foreign
Associate of the National Academy of Sciences in the United
States; an Honorary Fellow of The National Academy of Sciences,
India; a Foreign Honorary Member of the American Academy of
Arts and Sciences; an Honorary Member of the Japanese Biochemical
Society and a Fellow of the American Association for the Advancement
of Science.
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Kurt Wüthrich has won the 2002 Nobel Prize in Chemistry.
Photo by Alan McPhee.
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