-Seminars in Chemistry and Biochemistry at ASU

The first nuclear magnetic resonance (NMR) spectrum of a protein in solution was published in 1957. My own activities in this field started in 1967, and NMR spectroscopy in solution has been available as a second method, besides x-ray diffraction in single crystals, for three-dimensional structure determination of biological macromolecules since 1985. A first part of this lecture is devoted to a brief review of the current role of NMR in structural biology and structural proteomics. The main part of the lecture will then recount the technical developments in NMR spectroscopy, biochemistry and computational sciences that resulted in the present role of NMR in modern biological and biomedical research. This evolution of the method will be illusrated with research projects pursued in my laboratory at the ETH Zurich.

Friday, February 6, 2004 3:40 p.m., PS H-150

Until 1997, the use of solution NMR techniques was largely limited to molecular sizes well below 50’000 Da. This lecture will focus on new spectroscopic techniques that enable solution NMR studies with much larger molecular structures. The new experiments TROSY (transverse relaxation-optimized spectroscopy), which exploits cancellation of transverse relaxation effects during evolution periods and data acquisition by cross-correlated relaxation effects, and CRINEPT (cross-correlated relaxationenhanced polarization transfer), which makes further use of cross-correlated relaxation effects for improved efficiency of magnetization transfers in very large structures, have actually extended this size limit more than tenfold. Applications of these new techniques will be illustrated with studies of membrane proteins reconstituted in water-soluble detergent micelles.

Biographical Sketch of Kurt Wüthrich

Kurt Wüthrich is currently a Professor of Biophysics at the Eigenössiche Technische Hochschule (ETH) Zürich, Switzerland, and Cecil H. and Ida M. Green Visiting Professor of Structural Biology at The Scripps Research Institute (TSRI), La Jolla, California. His research interests are in molecular structural biology and in structural and functional proteomics. His specialty is nuclear magnetic resonance (NMR) spectroscopy with biological macromolecules, where he contributed the NMR method of three-dimensional structure determination of proteins and nucleic acids in solution. The Wüthrich group has solved more than 50 NMR structures of proteins and nucleic acids, including the immunosuppression system cyclophilin A-cyclosporin A, the homeodomainoperator DNA transcriptional regulatory system, and prion proteins from a variety of species. Born and educated in Switzerland, Dr. Wüthrich studied chemistry, physics and mathematics at the University of Bern from 1957-1962. In 1964 he obtained the Eidgenossiches Turn- und Sportlehrer diplom and a Ph.D. in inorganic chemistry with Prof. Silvio Fallab at the University of Basel. After receiving the Ph.D. he was a postdoctoral fellow in Basel with Prof. S. Fallab, at the University of California, Berkeley with Prof. R. E. Connick, and at Bell Telephone Laboratories in Murray Hill, New Jersey with Dr. R. G. Shulman. In 1969 he joined the faculty at ETH Zürich where he continues today. He served as Chairman of the Department of Biology from 1995-2000 and is currently Professor of Biophysics. Since 2001 he shares his time between the ETH and TSRI. Kurt Wüthrich’s achievements have been recognized with the awarding of the Prix Louis Jeantet de Médecine, the Kyoto Prize in Advanced Technology, the Nobel Prize in Chemistry, and by numerous other awards and honorary degrees.