The specificity of enzyme—substrate interactions



Molecules interact with one another. There is continual competition between their kinetic energies to be independent and the forces of intermolecular attraction to bring them together. Kinetic energies may dominate the interaction, such that molecules exist as gases with individual mobilities only slightly impaired by their environment. But even weak forces of attraction, less than 5 kJ mol-1, may be sufficient to encourage the formation of a fragile ‘complex’ such as an inert gas dimer, held together in loose geometrical configuration by dispersion or Van der Waals forces. At the other extreme, the strong interactions of a chemical bond, with a stabilization of 250 kJ mol-1 or more, may hold groups together with a specific, relatively rigid, geometry. Between these two limits are various interactions of intermediate strength which account for the cohesion and yet mobility of liquids, and for the existence of specific biologically important complexes such as those of antibody-antigen, hormone-receptor and enzyme-substrate.


Binding Energy Transition State Electrostatic Molecular Potential Entropy Loss Microscopic Rate Constant 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Albery, W. J. and Knowles, J. R. (1976) Evolution of enzyme functions and the development of catalytic efficiency. Biochemistry, 15, 5631–5640.CrossRefGoogle Scholar
  2. Bell, R. P., Critchlow, J. E. and Page, M. I. (1974) Ground state and transition state effects in the acylation of a-chymotrypsin in organic solvent water mixtures. J. Chem. Soc. Perkin Trans., 2, 245–249.Google Scholar
  3. Fersht, A. R. (1974) Catalysis, binding and enzyme-substrate complementarity. Proc. Roy. Soc. London B., 187, 397–407.CrossRefGoogle Scholar
  4. Fersht, A. R. (1977) Enzyme Structure and Mechanism, Freeman, San Francisco.Google Scholar
  5. Fersht, A. R. and Kaethner, M. M. (1976) Enzyme hyperspecificity. Rejection of threonine by the valyl-tRNA synthetase by misacylation and hydrolytic editing. Biochemistry, 15, 3342–3346.CrossRefGoogle Scholar
  6. Ferscht, A. R., Shi, J.-P., Wilkinson, et al. (1984) Analysis of enzyme structure and activity by protein engineering. Angew. Chem. Int. Ed. Engl., 23, 467–538.CrossRefGoogle Scholar
  7. Hol, W. G. T., van Duijnen, P. T. and Berendson, H. J. C. (1978) The a–helix dipole and properties of proteins. Nature, 273, 443–446.CrossRefGoogle Scholar
  8. Jencks, W. P. (1975) Binding energy, specificity and enzymic catalysis: the Circe effect. Adv. Enzymology, 43, 219–410.Google Scholar
  9. Jencks, W. P. (1980) In Molecular Biology, Biochemistry and Biophysics, Vol. 32 (eds F. Chapeville and A. L. Haenni), Springer-Verlag, New York, pp. 3–25.Google Scholar
  10. Jencks, W. P. (1981) On the attribution and additivity of binding energies. Proc. Natl Acad. Sci. USA, 78, 4046–4050.CrossRefGoogle Scholar
  11. Jencks, W. P. and Page, M. I. (1972) On the importance of togetherness in enzymic catalysis. Proc. Eighth FEBS Meeting Amsterdam, 29, 45–58.Google Scholar
  12. Kollman, P. A. (1977) Non-covalent interactions. Accounts Chem. Res., 10, 365–371.CrossRefGoogle Scholar
  13. Kollman, P. and Allen, L. C. (1972) Theory of hydrogen bonding. Chem. Rev., 72, 283–303.CrossRefGoogle Scholar
  14. Morokuma, K. (1977) Why do molecules interact? The origin of electron-donor- acceptor complexes, hydrogen bonding and proton affinity. Accounts Chem. Res., 10, 294–300.CrossRefGoogle Scholar
  15. Olovsson, I. and Jonsson, P. (1976) In The Hydrogen Bond - Recent Developments in Theory and Experiments (eds P. Schuster et al.), North-Holland, Amsterdam, pp. 394–456.Google Scholar
  16. Page, M. I. (1973) The energetics of neighbouring group participation. Chem. Soc. Rev., 2, 295–323.CrossRefGoogle Scholar
  17. Page, M. I. (1976) Binding energy and enzymic catalysis. Biochem. Biophys. Res. Commun., 72, 456–461.CrossRefGoogle Scholar
  18. Page, M. I. (1977) Entropy, binding energy and enzymic catalysis. Angewandte Chem. Int. Ed., 16, 449–459.CrossRefGoogle Scholar
  19. Page, M.I. (1979) The principles of enzymatic catalysis. Int. J. Biochem., 10, 471–476.CrossRefGoogle Scholar
  20. Page, M. I. (1984) The Chemistry of Enzyme Action, Elsevier Biomedical Press, Amsterdam.Google Scholar
  21. Page, M. I. and Jencks, W. P. (1971) Entropie contributions to rate accelerations in enzymic and intramolecular reactions and the chelate effect. Proc. Natl Acad. Sci. USA, 68, 1678–1683.CrossRefGoogle Scholar
  22. Pullman, A. and Berthod, H. (1978) Electrostatic molecular potentials in hydrogen bonded systems. Theoret. Chim. Acta, 48, 269–277.CrossRefGoogle Scholar
  23. Scrocco, E, and Tomasi, J.(1978)Electrostatic molecular potentials. Adv. in Quantum Chem., 11, 115–326.CrossRefGoogle Scholar
  24. Taylor, R. and Kennard, O. (1984) Hydrogen-bond geometry in organic crystals. Acc. Chem. Res., 17, 320–326.CrossRefGoogle Scholar
  25. Warshel, A. (1981) Electrostatic basis of structure-function correlation in proteins. Accounts Chem. Res., 14, 284–290.CrossRefGoogle Scholar

Copyright information

© Chapman and Hall 1986

Authors and Affiliations

There are no affiliations available

Personalised recommendations