Literature Seminar: abstract (Nov. 2000)

The qualitative way in which interatomic distances are derived from NOEs limits the accuracy at which the time-averaged conformation of biomolecules can be determined.¹ Moreover, the cumulative error in these local constraints can make it difficult to figure out the relative positions of structural elements with few connecting NOEs. In contrast, dipolar couplings provide direct information on the orientations of the bond vectors to the macromolecule's magnetic susceptibility tensor. Fundamental difference between NOEs and Dipolar Couplings gives a possibility to extract the structural information with high accuracy.

However, several problems make a reliable extraction of structural information from dipolar couplings for macromolecules problematic in the solid state. Alternatively, rotational diffusion averages dipolar couplings to zero in liquids. A new approach makes it possible to measure dipolar couplings for fairly large proteins that are partially oriented in liquid crystalline phases. Liquid crystal solvents² allow one to observe nuclear dipolar coupling constants, and from these, derive molecular structural information.³ The first report of a high resolution NMR spectrum of a liquid crystal solution was in 1964. In the past decade measurements of ¹³C-¹³C, ¹³C-¹H,^{4 15}N-¹H, and particularly ¹⁵N-¹³C dipolar couplings have become robust⁵ even for relatively large bio-molecules such as ubiquitin.

References

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2. Ramirez B.E.; Bax A. J. Am. Chem. Soc. 1998, 120, 9106-9107.
3. Emsley J.W.; Lindon J.C. NMR Spectroscopy Using Liquid Crystal Solvents; Pergamon: New-York, 1975; Chapter 1.
4. Ottiger M.; Bax A. J. Am. Chem. Soc. 1999, 121, 4690-4695.
5. Clore, G.M.; Gronenborn, A.M.; Bax, A. J. Magn. Reson. 1998, 133, 216.
6. Ottiger M.; Bax A. J. Am. Chem. Soc. 1998, 120, 12334-12341.
7. Fischer M.W.F.; Losoczi J.A.; Weaver J.L.; Prestegard J.H. Biochemistry 1999, 38 (28), 9013-9022.
8. Delaglio F.; Kontaxis G.; Bax A. J. Am. Chem. Soc. 2000, 122, 2142-2143.