NMR Comes of Age with Nobel Recognition
"Nuclear magnetic resonance (NMR) has long been in the shadow
of crystallography," says Peter Wright, Cecil H. and Ida M.
Green Investigator in Medical Research and chair of the Department
of Molecular Biology at The Scripps Research Institute (TSRI).
The 2002 Nobel Prize in Chemistry should change that. It
was awarded to Kurt Wüthrich for "his development of
nuclear magnetic resonance spectroscopy for determining the
three-dimensional structure of biological macromolecules in
solution."
Of the two primary methods for determining the three-dimensional
structure of biological macromolecules—x-ray crystallography
and NMR—crystallography is older by several decades.
NMR exploded on the scene in the early 1980s as a viable technique
for biomolecular structure determination when Wüthrich
worked out the methodologies needed to solve the first protein
structures using NMR.
Around the same time that Wüthrich was beginning to
solve his first structures with the method, NMR was arriving
at TSRI with Wright and Professor H. Jane Dyson, who came
to the institute in 1984. NMR has been a part of the structural
biology research at TSRI ever since.
"The NMR group here is incredibly strong," says Wright.
"And we have one of the biggest and best-equipped NMR facilities
in the world."
The principle NMR structural biologists at TSRI are:
H. Jane Dyson, who uses NMR to study the protein-folding
process and the nature and behavior of unfolded and partly
folded forms of proteins, including prion proteins and several
newly-discovered, intrinsically unstructured proteins.
Mirko Hennig, who develops new NMR methodology to
study the structure and dynamics of RNA and RNA–protein
complexes. Mirko is particularly interested in using novel
isotope labeling methodology in conjunction with tailored
NMR experiments to provide new avenues to determine the structure
of very large RNA molecules.
James R. Williamson, who studies the structure and
dynamics of RNA molecules and RNA-protein complexes involved
in the regulation of gene expression by employing NMR spectroscopy
and X-ray crystallography for solving high-resolution three-dimensional
structures and examining the mechanism of assembly of multiprotein-RNA
complexes.
Peter Wright, who uses high-resolution, multi-dimensional,
hetero-nuclear NMR spectroscopy to study protein and enzyme
dynamics, protein folding, and molecular recognition. In particular,
his laboratory solves structures of many protein-DNA and protein-protein
complexes involved in the regulation of transcription.
Kurt Wüthrich, who develops NMR methodologies,
pioneering the new techniques of transverse relaxation-optimized
spectroscopy NMR (TROSY) and cross-correlated relaxation-enhanced
polarization transfer (CRINEPT), which extend several-fold
the size limit of structures that can be solved with NMR.
In addition, he solves many structures of biological molecules—including
pheromone, prion, and membrane proteins.
"Kurt's prize is extremely important because it is recognition
for NMR as a method for determining the structures of biological
macromolecules in solution," says Wright. "It really puts
the field on the map, and having him join the group of NMR
structural biologists at TSRI brings additional strength to
what was already a world-class operation."
Wüthrich is Cecil H. and Ida M. Green Visiting Professor
of Structural Biology in the Department of Molecular Biology
at The Scripps Research Institute (TSRI); a member of TSRI's
Skaggs Institute for Chemical Biology; and Professor of Biophysics
at Eidgenössische Technische Hochschule Zürich (ETHZ)
in Switzerland.
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