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  The Nobel Prize in Chemistry 2002
       
  NMR:
To understand, we need to see
 

With NMR the three-dimensional structure of different substances can be studied. Unlike the alternative method, X-ray crystallography, NMR can be applied to molecules in solution. This is a great advantage since the natural environment of the protein is the living cell.

In NMR the sample is placed in a strong magnetic field. Pulses of radio waves are beamed into the sample, the atoms of which "answer" by emitting new radio waves. The result is a spectrum in which each atomic nucleus causes one or more peaks. This is because the magnetic field around each atom is affected by its neighbouring atoms. A large protein gives rise to a very complicated spectrum with numerous peaks.

       
  Many peaks in the spectrum – no problem!    
 

Kurt Wüthrich had an idea for how to find out which peaks correspond to which atoms. His method is called sequential assignment. It involves starting with a signal from a known atomic nucleus and then finding the nucleus in the peptide chain that is signalling that it is a neighbour of the first. Wüthrich matched each signal successively with its atom. With a similar method, which senses the distance between nuclei, he then determined a large number of pairwise distances in the protein, which gave the three-dimensional structure of that protein.

The different nuclei are identified one after the other in a two-dimensional NMR spectrum, here in a composite diagram in which one can navigate between 'cross-peaks' that signal atom proximity.

 

If one knows all the measurements of a house one can draw a three-dimensional picture of that house. In the same way, by measuring a vast number of short distances in a protein, it is possible to create a three-dimensional picture of that protein.

     
   

Kurt Wüthrich preparing a protein solution in an NMR tube. His measurement gives a three-dimensional picture of the protein structure in solution. Wüthrich works at ETH in Zürich, Switzerland and at the Scripps Research Institute, La Jolla, USA.

 



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