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A conformational study of the tetrapeptide CH3CO-Ala-Asp-Gly-Lys-NHCH3 corresponding to a β-bend in staphylococcal nuclease

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Abstract

The tetrapeptide sequence Ala-Asp-Gly-Lys occurs as a type I′ β-bend at residues 94–97 in staphylococcal nuclease. We have synthesized theN-acetyl,N′-methylamide derivative of this tetrapeptide and studied its conformation in solution, using nuclear magnetic resonance (NMR) and circular dichroism (CD) spectroscopy. In the synthesis, special attention was paid to the possibility of cyclic aspartimide formation giving rise to mixtures of α- and β-Asp-Gly products. The presence of such a mixture was excluded by infrared, NMR, and other analytical procedures applied to the products and to models for α- and β-linked aspartyl residues. The CD spectra of the protected tetrapeptide in water, methanol, and trifluoroethanol show no evidence of preferred chain conformations. In dimethylsulfoxide-d6, however, the NMR spectra are consistent with the presence of a population of conformers in which the Lys and C-terminal NHCH3 amide protons are shielded from solvent. Taken together with the observed3JNH-C α H coupling constants for all residues, this permitted the construction and energetic evaluation of possible conformations in solution. Only one such conformation was fully compatible with the NMR data; this is a type II β-bend in which the Lys and C-terminal NHCH3 amide protons are close to the Ala C=O group and may form bifurcated hydrogen bonds with it. This conformation can be converted into the conformation existing in staphylococcal nuclease by rotating the plane of the Ala-Asp peptide group by about 120° around a line connecting the Ala and Asp Cα atoms and by making small shifts in dihedral angles elsewhere in the peptide.

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References

  • Anderson, G. W., Zimmerman, J. E., and Callahan, F. M. (1964).J. Am. Chem. Soc. 86, 1839–1842.

    Article  CAS  Google Scholar 

  • Anteunis, M. J. O. (1977).Tetrahedron Lett. 1977, 1535–1538.

    Article  Google Scholar 

  • Arnone, A., Bier, C. J., Cotton, F. A., Day, V. W., Hazen, E. E., Jr., Richardson, D. C., Richardson, J. S., and Yonath, A. (1971).J. Biol. Chem. 246, 2302–2316.

    Article  CAS  PubMed  Google Scholar 

  • Aubry, A., Protas, J., Boussard, G., Marraud, M., and Néel, J. (1978).Biopolymers 17, 1693–1711.

    Article  CAS  Google Scholar 

  • Bandekar, J., Evans, D. J., Krimm, S., Leach, S. J., Lee, S., McQuie, J. R., Minasian, E., Némethy, G., Pottle, M. S., Scheraga, H. A., Stimson, E. R., and Woody, R. W. (1982).Int. J. Peptide Protein Res. 19, 187–205.

    Article  CAS  Google Scholar 

  • Battersby, A. R., and Robinson, J. C. (1955).J. Chem. Soc. 1955, 259–269.

    Article  Google Scholar 

  • Bavoso, A., Benedetti, E., Di Blasio, B., Pavone, V., Pedone, C., Lorenzi, G. P., and Muri-Valle, V. (1982).Biochem. Biophys. Res. Commun. 107, 910–913.

    Article  CAS  PubMed  Google Scholar 

  • Bellamy, L. J. (1975). InThe Infra-Red Spectra of Complex Molecules, 3rd ed., Chapman and Hall, London, pp. 247–248.

    Book  Google Scholar 

  • Bleich, H. E., Day, A. R., Freer, R. J., and Glasel, J. A. (1977).Biochem. Biophys. Res. Commun. 74, 592–598.

    Article  CAS  PubMed  Google Scholar 

  • Bodanszky, M., and Kwei, J. Z. (1978).Int. J. Peptide Protein Res. 12, 69–74.

    Article  CAS  Google Scholar 

  • Bodanszky, M., and Martinez, J. (1981).Synthesis 1981, 333–356.

    Article  Google Scholar 

  • Bodanszky, M., Ondetti, M. A., Levine, S. D., and Williams, N. J. (1967).J. Am. Chem. Soc. 89, 6753–6757.

    Article  CAS  PubMed  Google Scholar 

  • Bodanszky, M., Sigler, G. F., and Bodanszky, A. (1973).J. Am. Chem. Soc. 95, 2352–2357.

    Article  CAS  PubMed  Google Scholar 

  • Bodanszky, M., Tolle, J. E., Deshmane, S. S., and Bodanszky, A. (1978).Int. J. Peptide Protein Res. 12, 57–68.

    Article  CAS  Google Scholar 

  • Bovey, F. A., Brewster, A. I., Patel, D. J., Tonelli, A. F., and Torchia, D. A. (1972).Acc. Chem. Res. 5, 193–200.

    Article  CAS  Google Scholar 

  • Brahmachari, S. K., Ananthanarayanan, V. S., Brahms, S., Brahms, J., Rapaka, R. S., and Bhatnagar, R. S. (1979).Biochem. Biophys. Res. Commun. 86, 605–612.

    Article  CAS  PubMed  Google Scholar 

  • Brahms, S., Brahms, J., Spach, G., and Brack, A. (1977).Proc. Natl. Acad. Sci. USA 74, 3208–3212.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bundi, A., and Wüthrich, K. (1979).Biopolymers 18, 285–297.

    Article  CAS  Google Scholar 

  • Bundi, A., Grathwohl, C., Hochmann, J., Keller, R. M., Wagner, G., and Wüthrich, K. (1975).J. Magn. Reson. 18, 191–198.

    CAS  Google Scholar 

  • Bush, C. A., Sarkar, S. K., and Kopple, K. D. (1978).Biochemistry 17, 4951–4954.

    Article  CAS  PubMed  Google Scholar 

  • Bystrov, V. F. (1976).Progr. NMR Spectroscopy 10, 41–81.

    Article  Google Scholar 

  • Cookson, R. C., Crabb, T. A., Frankel, J. J., and Hudec, J. (1966).Tetrahedron Suppl. 7, 355–390.

    Article  CAS  Google Scholar 

  • Deslauriers, R., Evans, D. J., Leach, S. J., Meinwald, Y. C., Minasian, E., Némethy, G., Rae, I. D., Scheraga, H. A., Somorjai, R. L., Stimson, E. R., Van Nispen, J. W., and Woody, R. W. (1981).Macromolecules 14, 985–996.

    Article  CAS  Google Scholar 

  • Fasman, G. D., Hoving, H., and Timasheff, S. N. (1970).Biochemistry 9, 3316–3324.

    Article  CAS  PubMed  Google Scholar 

  • Glasoe, P. K., and Long, F. A. (1960).J. Phys. Chem. 64, 188–190.

    Article  CAS  Google Scholar 

  • Howard, J. C., Ali, A., Scheraga, H. A., and Momany, F. A. (1975).Macromolecules 8, 607–622.

    Article  CAS  PubMed  Google Scholar 

  • Isogai, Y., Némethy, G., Rackovsky, S., Leach, S. J., and Scheraga, H. A. (1980).Biopolymers 19, 1183–1210.

    Article  CAS  PubMed  Google Scholar 

  • Kawai, M., and Fasman, G. (1978).J. Am. Chem. Soc. 100, 3630–3632.

    Article  CAS  Google Scholar 

  • Khaled, M. A., Urry, D. W., and Okamoto, K. (1976).Biochem. Biophys. Res. Commun. 72, 162–169.

    Article  CAS  PubMed  Google Scholar 

  • Kopple, K. D., Go, A., Logan, R. H. Jr., and Šavrda, J. (1972).J. Am. Chem. Soc. 94, 973–981.

    Article  CAS  PubMed  Google Scholar 

  • Laufer, D. A., and Blout, E. R. (1967).J. Am. Chem. Soc. 89, 1246–1249.

    Article  CAS  PubMed  Google Scholar 

  • Leach, S. J., Evans, D. J., Minasian, E., and Sikaris, K. (1983).J. Protein Chem., in preparation.

  • Lewis, P. N., Momany, F. A., and Scheraga, H. A. (1973).Biochim. Biophys. Acta 303, 211–229.

    Article  CAS  PubMed  Google Scholar 

  • Manning, J. M., and Moore, S. (1968).J. Biol. Chem. 243, 5591–5597.

    Article  CAS  PubMed  Google Scholar 

  • Momany, F. A., McGuire, R. F., Burgess, A. W., and Scheraga, H. A. (1975).J. Phys. Chem. 79, 2361–2381.

    Article  CAS  Google Scholar 

  • Némethy, G., and Scheraga, H. A. (1977).Q. Rev. Biophys. 10, 239–352.

    Article  PubMed  Google Scholar 

  • Némethy, G., and Scheraga, H. A. (1980).Biochem. Biophys. Res. Commun. 95, 320–327.

    Article  PubMed  Google Scholar 

  • Némethy, G., Miller, M. H., and Scheraga, H. A. (1980).Macromolecules 13, 914–919.

    Article  Google Scholar 

  • Némethy, G., Pottle, M. S., and Scheraga, H. A. (1983).J. Phys. Chem., manuscript submitted.

  • Nicola, N. A., Minasian, E., Appleby, C. A., and Leach, S. J. (1975).Biochemistry 14, 5141–5149.

    Article  CAS  PubMed  Google Scholar 

  • Ondetti, M. A., Deer, A., Sheehan, J. T., Pluscec, J., and Kocy, O. (1968).Biochemistry 7, 4069–4075.

    Article  CAS  PubMed  Google Scholar 

  • Powell, M. J. D. (1964).Computer J. 7, 155–162.

    Article  Google Scholar 

  • Rivier, J. P. (1978).J. Liquid Chromatography 1, 343–366.

    Article  CAS  Google Scholar 

  • Simon, I., Némethy, G., and Scheraga, H. A. (1978).Macromolecules 11, 797–804.

    Article  CAS  Google Scholar 

  • Toma, F., Lan-Thanh, H., Piriou, F., Heindl, M.-C., Lintner, K., and Fermandjian, S. (1980).Biopolymers 19, 781–804.

    Article  CAS  Google Scholar 

  • Toniolo, C., and Bonora, G. M. (1976).Can. J. Chem. 54, 70–76.

    Article  CAS  Google Scholar 

  • Urry, D. W., Ohnishi, M., and Walter, R. (1970).Proc. Natl. Acad. Sci. USA 66, 111–116.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Urry, D. W., Long, M. M., Ohnishi, T., and Jacobs, M. (1974).Biochem. Biophys. Res. Commun. 61, 1427–1433.

    Article  CAS  PubMed  Google Scholar 

  • Venkatachalam, C. M. (1968).Biopolymers 6, 1425–1436.

    Article  CAS  PubMed  Google Scholar 

  • Woody, R. W. (1974). InPeptides, Polypeptides and Proteins, Blout, E. R., Bovey, F. A., Goodman, M., and Lotan, N. (eds.), Wiley, New York, pp. 338–350.

    Google Scholar 

  • Yang, C. C., and Merrifield, R. B. (1976).J. Org. Chem. 41, 1032–1041.

    Article  CAS  PubMed  Google Scholar 

  • Zimmerman, S. S., Pottle, M. S., Némethy, G., and Scheraga, H. A. (1977).Macromolecules 10, 1–9.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Division of Textile Industry, CSIRO, Belmont, Victoria, Australia

    D. J. Evans

  2. Department of Chemistry, Monash University, Clayton, Victoria, Australia

    I. D. Rae

  3. Russell Grimwade School of Biochemistry, University of Melbourne, Parkville, Victoria, Australia

    E. Minasian & S. J. Leach

  4. Baker Laboratory of Chemistry, Cornell University, Ithaca, New York

    G. Némethy & H. A. Scheraga

Authors
  1. D. J. Evans
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  2. I. D. Rae
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  3. E. Minasian
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  4. G. Némethy
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  5. H. A. Scheraga
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  6. S. J. Leach
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Evans, D.J., Rae, I.D., Minasian, E. et al. A conformational study of the tetrapeptide CH3CO-Ala-Asp-Gly-Lys-NHCH3 corresponding to a β-bend in staphylococcal nuclease. J Protein Chem 2, 77–99 (1983). https://doi.org/10.1007/BF01025169

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  • DOI: https://doi.org/10.1007/BF01025169

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