Abstract
Although the majority of the ion pairs found in proteins consists of two charges of opposite sign, the observation of some unusual arrangements of two arginines led us to a search of such occurrences in the Brookhaven Protein Data Bank. We have found 41 Arginine-Arginine interactions with a Cζ...Cζ distance less than 5 å. Computer graphics analysis of these structures shows that most of the Arg-Arg pairs are found in the vicinity of the surface of the proteins, in an easily hydrated region. In order to determine which factors could stabilize such arrangements of species of similar charge, we have carried out AM1 semi-empirical calculations on a model of two guanidinium ions surrounded by several water molecules. The results show the existence of stable clusters with six or more water molecules, with distances between Cζ atoms around 3 å. The bridging role of the water molecules is an important structural and energetic feature and we find bridges of two and three molecules between the guanidinium ions. These results are in good agreement with the structures found in our search of the experimental data. Enhancement of the electrostatic potential around these clusters, when compared to one of the guanidinium ions alone, is also demonstrated.
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Arnold, E., Vriend, G., Luo, M., Griffith, J. P., Kramer, G., Erickson, J. W., Johnson, J. E., and Rossman, M. G. (1987).Acta Crystallogr. sect. A. 43, 346–361.
Baker, E. N., and Hubbard, R. E. (1984).Prog. Biophys. Molec. Biol. 44, 97–179.
Baldwin, J. M. (1975).Prog. Biophys. Mol. Biol. 29, 225–320.
Bernstein, F. C., Koetzle, T. F., Williams, G. J. B., Meyer, E. F., Jr., Brice, M. D., Rodgers, J. R., Kennard, O., Shimanouchi, T., and Tasumi, M. (1977).J. Mol. Biol. 112, 535–542.
Boudon, S., Wipff, G., and Maigret, B. (1990).J. Phys. Chem. 94, 6056–6061.
Bray, D. D., Slattery, N., and Russell, C. S. (1984).Int. J. Peptide Protein Res. 24, 414–418.
Brooks, C. L., Karplus, M., and Pettitt, B. M. (1988).Adv. Chem. Phys. 71, 137–175.
Brünger, A. T., Brooks, C. L., and Karplus, M. (1985).Proc. Natl. Acad. Sci. USA 82, 8458–8462.
Cramer, C. J., and Truhlar, D. G. (1991).J. Am. Chem. Soc. 113, 8305–8311.
Dannenberg, J. J., and Vinson, L. K. (1988).J. Phys. Chem. 92, 5635–5639.
Davies, D. R., Padlan, E. A., and Sheriff, S. (1990).Annu. Rev. Biochem. 59, 439–473.
Davidon, W. C. (1969).Computer Journal 10, 406–410.
Dean, P. N. (1987).Molecular Foundations of Drug-Receptor Interaction, Cambridge U. Press, Cambridge.
Dewar, M. J. S., Zoebisch, E. G., Healy, E. F., and Stewart, J. J. P. (1985).J. Am. Chem. Soc. 107, 3902–3909.
Fletcher, R., and Powell, M. J. D. (1963).Computer Journal 6, 163–168.
Gao, J., Boudon, S., and Wipff, G. (1991).J. Am. Chem. Soc. 113, 9610–9614.
Getzoff, E. D., Tainer, J. A., Weiner, P. K., Kollman, P. A., Richardson, J. S., and Richardson, D. C. (1983).Nature 306, 287–290.
Horovitz, A., Serrano, L., Avron, B., Bycroft, M., and Fersht, A. R. (1990).J. Mol. Biol. 216, 1031–1044.
Jeffrey, G. A., and Mitra, J. (1984).J. Am. Chem. Soc. 106, 5546–5553.
Kistenmacher, H., Popkie, H., and Clementi, E. (1973).J. Chem. Phys. 58, 5627–5638.
Lehmann, M. S., Verbist, J. J., Hamilton, W. C., and Koetzle, T. F. (1973).J. Chem. Soc.-Perkin II 133–137.
Liotard, D. A., Healy, E. F., Ruiz, J. M., and Dewar, M. J. S. (1989). AMPAC, version 2.1, QCPE program number 506.
Mitchell, J. B. O., Thornton, J. M., and Singh, J. (1992).J. Mol. Biol. 226, 251–262.
Mrabet, N. T., Van den Broeck, A., Van den Brande, I., Stanssens, P., Laroche, Y., Lambeir, A.-M., Matthijssens, G., Jenkins, J., Chiadmi, M., van Tilbeurgh, H., Rey, F., Janin, J., Quax, W. J., Lasters, I., de Maeyer, M., and Wodak, S. J. (1992).Biochemistry 31, 2239–2253.
Perrin, C. L., and Gipe, R. K. (1986).J. Am. Chem. Soc. 108, 1088–1089.
Perutz, M. F. (1978).Science 201, 1187–1191.
Pettitt, B. M., and Rossky, P. J. (1986).J. Chem. Phys. 84, 5836–5844.
Sapse, A. M., and Massa, L. J. (1980).J. Org. Chem. 45, 719–721.
Schultz, P. G. (1989).Acc. Chem. Res. 22, 287–294.
Sheridan, R. P., and Allen, L. C. (1981).J. Am. Chem. Soc. 103, 1544–1550.
Sheriff, S., Silverton, E. W., Padlan, E. A., Cohen, G. H., Smith-Gill, S. J., Finzel, B. C., and Davies, D. R. (1987).Proc. Natl. Acad. Sci. USA 84, 8075–8079.
Singh, J., Thornton, J. M., Snarey, M., and Campbell, S. F. (1987).FEBS Letters 224, 161–171.
Singh, J., and Thornton, J. M. (1992).Atlas of Protein Side-Chain Interactions, IRL Press, Oxford, UK.
Sternberg, M. J. E., Hayes, F. R. F., Russell, A. J., Thomas, P. G., and Fersht, A. R. (1987).Nature 330, 86–88.
Stewart, J. J. P. (1990). MOPAC, version 6.0, QCPE program number 455.
Sutton, L. E. (1965). Tables of Interatomic Distances and Configuration in Molecules and Ions, Supplement 1956–1959, London, The Chemical Society, Burlington House, W.1.
Van Belle, D., Couplet, I., Prevost, M., and Wodak, S. J. (1987).J. Mol. Biol. 198, 721–735.
Warshel, A. (1981).Acc. Chem. Res. 14, 284–290.
Warshel, A., and Russell, S. T. (1984).Quarterly Rev. Biophys. 17, 283–422.
Warshel, A. (1987).Nature 330, 15–16.
Weaver, D. F., Khalil, M., and Smith, Jr. V. H. (1991).J. Mol. Struct. 226, 73–86.
Williams, M. L., and Gready, J. E. (1989).J. Comp. Chem. 10, 35–54.
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Magalhaes, A., Maigret, B., Hoflack, J. et al. Contribution of unusual Arginine-Arginine short-range interactions to stabilization and recognition in proteins. J Protein Chem 13, 195–215 (1994). https://doi.org/10.1007/BF01891978
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DOI: https://doi.org/10.1007/BF01891978