Refinement of Three-Dimensional Protein and DNA Structures in Solution from NMR Data

  • Thomas L. James
  • Miriam Gochin
  • Deborah J. Kerwood
  • David A. Pearlman
  • Uli Schmitz
  • Paul D. Thomas
Part of the NATO ASI Series book series (NSSA, volume 225)


Two-dimensional NMR, in particular two-dimensional nuclear Overhauser effect (2D NOE) spectra, when used in conjunction with distance geometry and energy refinement calculations can be used to determine the high-resolution structure of DNA fragments and small proteins. To understand functional interactions of proteins and nucleic acids, it is important to know their solution structures to high-resolution. Problems addressed with DNA structure and with protein structure studies are often of a different nature. In general, we are interested in fairly subtle structural changes in the DNA helix which are sequence-dependent and, consequently, guide protein, mutagen or drug recognition. These subtle variations demand detailed knowledge of the structure and, therefore, accurate internuclear distance and perhaps torsion angle constraints. But one can define a protein tertiary structure with moderate accuracy using distance geometry or restrained molecular dynamics calculations without accurately determining interproton distances; a qualitative assessment of 2D NOE intensities is often all that is needed. However, in proteins possessing less common structural features, it may be especially valuable to have additional structural constraints and more accurate constraints for use with the computational techniques. And, even more importantly, we will want better defined structures at ligand binding sites (with and without ligand bound).


Torsion Angle Cross Peak Distance Geometry Interproton Distance Vicinal Coupling Constant 
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  1. 1.
    B. A. Borgias and T. L. James, J. Magn. Reson. 79, 493–512 (1988).Google Scholar
  2. 2.
    J. W. Keepers and T. L. James, J. Magn. Reson. 57, 404–426 (1984).Google Scholar
  3. 3.
    B. A. Borgias and T. L. James, J. Magn. Reson. 87, 475–487 (1990).Google Scholar
  4. 4.
    R. Boelens, T. M. G. Koning, and R. Kaptein, J. Mol. Struc. 173, 299–311 (1988).CrossRefGoogle Scholar
  5. 5.
    B. A. Borgias and T. L. James, in “Methods in Enzymology, Nuclear Magnetic Resonance, Part A: Spectral Techniques and Dynamics,” N. J. Oppenheimer and T. L. James, ed., vol. 176, pp. 169–183, Academic Press, New York (1989).CrossRefGoogle Scholar
  6. 6.
    H. Widmer and K. Wüthrich, J. Magn. Reson. 74, 316–336 (1987).Google Scholar
  7. 7.
    U. Schmitz, G. Zon, and T. L. James, Biochemistry 29, 2357–2368 (1990).PubMedCrossRefGoogle Scholar
  8. 8.
    S. Macura, and R. R. Ernst, Mol. Phys. 41, 95–117 (1980).CrossRefGoogle Scholar
  9. 9.
    T. E. Bull, J. Magn. Reson. 72, 397–413 (1987).Google Scholar
  10. 10.
    L. Werbelow and D. M. Grant, Adv. Magn. Reson. 9, 189 (1978).Google Scholar
  11. 11.
    L. E. Kay, T. A. Holak, B. A. Johnson, I. M. Armitage, and J. H. Prestegard, J. Am. Chem. Soc. 108, 4242–4244 (1986).CrossRefGoogle Scholar
  12. 12.
    T. L. James, D. J. Kerwood, M. Gochin, P. A. Mills, B. A. Borgias, and V. J. Basus, 1991, in “Fourth Cyprus Conference on New Methods in Drug Research, Proceedings,” Makriannis, A., ed., in press, Pergamon Press, Oxford.Google Scholar
  13. 13.
    R. Boelens, T. M. G. Koning, G. A. van der Marel, J. H. van Boom, R. Kaptein, J. Magn. Reson. 82, 290–308 (1989).Google Scholar
  14. 14.
    B. A. Borgias, M. Gochin, D. J. Kerwood, and T. L. James, in “Progress in Nuclear Magnetic Resonance Spectroscopy,” J. W. Emsley, J. Feeney, and L. H. Sutcliffe, eds., vol. 22, pp. 83–100, Pergamon Press, Oxford (1990).Google Scholar
  15. 15.
    E.-I. Suzuki, N. Pattabiraman, G. Zon, and T. L. James, Biochemistry 25, 6854–6865 (1986).PubMedCrossRefGoogle Scholar
  16. 16.
    N. Zhou, A. M. Bianucci, N. Pattabiraman, and T. L. James, Biochemistry 26, 7905–7913 (1987).PubMedCrossRefGoogle Scholar
  17. 17.
    W. C. Hamilton, “Statistics in Physical Science,” Ronald Press, New York (1964).Google Scholar
  18. 18.
    U. C. Singh, P. K. Weiner, J. Caldwell, and P. A. Kollman, “AMBER 3.0,” University of California, San Francisco (1986).Google Scholar
  19. 19.
    P. K. Weiner, and P. A. Kollman, J. Comp, Chem. 2, 287–303 (1981).CrossRefGoogle Scholar
  20. 20.
    S. J. Weiner, P. A. Kollman, D. T. Nguyen, and D. A. Case, J. Comp. Chem. 7, 230–252 (1986).CrossRefGoogle Scholar
  21. 21.
    N. Zhou, S. Manogaran, G. Zon, and T. L. James, Biochemistry 27, 6013–6020 (1988).PubMedCrossRefGoogle Scholar
  22. 22.
    B. Celda, H. Widmer, W. Leupin, W. J. Chazin, W. A. Denny, and K. Wüthrich, Biochemistry 28, 1462–1470 (1989).PubMedCrossRefGoogle Scholar
  23. 23.
    C. Altona and M. Sundaralingam, J. Am. Chem. Soc. 94, 8205–8212 (1972).PubMedCrossRefGoogle Scholar
  24. 24.
    C. A. G. Haasnoot, F. A. A. M. de Leeuw, H. P. M. de Leeuw, and C. Altona, Org. Magn., Reson. 15, 43–52 (1981).CrossRefGoogle Scholar
  25. 25.
    L. J. Rinkel, and C. Altona, J. Biomol. Struct. Dyn. 4, 621–649 (1987).PubMedCrossRefGoogle Scholar
  26. 26.
    F. A. A. M. de Leeuw and C. Altona, J. Comp. Chem. 4, 428–437 (1983).CrossRefGoogle Scholar
  27. 27.
    M. Gochin, G. Zon, and T. L. James, Biochemistry 29, 11161–11171 (1990).PubMedCrossRefGoogle Scholar
  28. 28.
    M. Gochin, and T. L. James, Biochemistry, 29, 11172–11180 (1990).PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1991

Authors and Affiliations

  • Thomas L. James
    • 1
  • Miriam Gochin
    • 1
  • Deborah J. Kerwood
    • 1
  • David A. Pearlman
    • 1
  • Uli Schmitz
    • 1
  • Paul D. Thomas
    • 1
  1. 1.Department of Pharmaceutical ChemistryUniversity of CaliforniaSan FranciscoUSA

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