Kurt Wüthrich, a prominent Swiss chemist, revolutionized the understanding of biological macromolecules, particularly proteins. He introduced innovative methods for deciphering their three-dimensional structures, profoundly influencing modern scientific research.
A Life Dedicated to Science
Born in Aarberg, Switzerland, in 1938, Kurt Wüthrich developed an early interest in natural science. He pursued his academic journey at the University of Bern, studying chemistry, physics, and mathematics. He earned his Ph.D. in organic chemistry from the University of Basel in 1964.
Following his doctoral studies, Wüthrich undertook postdoctoral work at the University of California, Berkeley, where he began exploring nuclear magnetic resonance (NMR) spectroscopy. He then spent two years at Bell Telephone Laboratories in New Jersey, applying NMR to proteins. In 1969, he returned to Switzerland, joining ETH Zurich, where he became a professor of biophysics by 1980.
Unlocking Protein Structures with NMR
Wüthrich pioneered the adaptation of Nuclear Magnetic Resonance (NMR) spectroscopy to determine the three-dimensional structures of biological macromolecules in solution. Previously, X-ray crystallography was the primary method for protein structure determination, requiring proteins to be crystallized. However, many proteins are difficult to crystallize, and X-ray crystallography provides a static view, whereas proteins in biological systems are dynamic.
He overcame the challenge of interpreting complex NMR signals by introducing the “sequential assignment” method. This technique systematically matches each NMR signal to a specific hydrogen nucleus within the protein. This allowed for the determination of distances between pairs of hydrogen nuclei. These distance restraints are then used in computer calculations to build a three-dimensional model of the protein. The first complete protein structure determined by Wüthrich’s NMR method was the bull seminal protease inhibitor in 1984.
The Broader Scientific Impact
Wüthrich’s development of NMR methods for proteins had a significant impact on structural biology and related fields. His work provided a way to study proteins in a solution-based environment, offering insights into their dynamic behaviors and conformational changes. This capability enabled a deeper understanding of how proteins function, interact with other molecules, and their roles in various biological processes.
The ability to visualize protein structures in solution has been beneficial for understanding disease mechanisms. For example, NMR structures have been instrumental in designing drugs to treat conditions like cancer and HIV. His methods also contributed to studies of protein folding, transcriptional regulation, and immunosuppression. Wüthrich’s laboratory has determined over 50 novel NMR structures of proteins and nucleic acids, including human and bovine prion proteins.
Nobel Recognition and Legacy
Kurt Wüthrich was awarded the Nobel Prize in Chemistry in 2002. He shared the prize with John B. Fenn and Koichi Tanaka, who were recognized for their work on mass spectrometry for biological macromolecules. Wüthrich’s specific recognition was “for his development of nuclear magnetic resonance spectroscopy for determining the three-dimensional structure of biological macromolecules in solution.”
His contributions remain fundamental tools in laboratories worldwide. He also pioneered transverse relaxation-optimized spectroscopy (TROSY), which expanded the size limit of molecules that could be studied with NMR. Wüthrich continues his research at institutions like ETH Zurich and The Scripps Research Institute, focusing on areas such as G protein-coupled receptors and healthcare in aging societies.