Pseudocontact shifts in biomolecular NMR using paramagnetic metal tags

Studying proteins with the help of paramagnetic lanthanide ions is becoming increasingly popular. By choosing the attachment sites of paramagnetic tags, it is possible to study such protein properties site-selectively without having to solve again the 3D structure of the entire protein, as required in X-ray crystallography or cryo-electron microscopy. In particular, owing to the long-range nature of paramagnetic effects, lanthanide tags lend themselves to site-specific studies where the tag must be sufficiently far from the site of interest not to interfere. To support site-specific NMR studies, it will be useful to develop improved methods for labeling the site of interest with NMR isotopes, e.g. by segmental isotopic labeling or residue-specific labeling. In view of the general importance of NMR spectroscopy in drug development, the availability of protein crystal structures also provides fertile ground for further developments of lanthanide tagging techniques to support fragment-based drug design.