Abstract
The role of complementary hydrogen bonding as a determinant of biological specificity has been examined by protein engineering of the tyrosyl-tRNA synthetase. Deletion of a side chain between enzyme and substrate to leave an unpaired, uncharged hydrogen-bond donor or acceptor weakens binding energy by only 0.5–1.5 kcal mol−1. But the presence of an unpaired and charged donor or acceptor weakens binding by a further ∼3 kcal mol−1.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 51 print issues and online access
$199.00 per year
only $3.90 per issue
Buy this article
- Purchase on SpringerLink
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Kauzmann, W. Adv. Protein Chem. 14, 1–63 (1959).
Klotz, I. M. & Franzen, J. S. J. Am. chem. Soc. 84, 3461–3466 (1962).
Cantor, C. R. & Schimmel, P. R. Biophysical Chemistry pt 1, 277 (Freeman, San Francisco, 1980).
Fersht, A. R. & Jakes, R. Biochemistry 14, 3350–3356 (1975).
Wilkinson, A. J., Fersht, A. R., Blow, D. M. & Winter, G. Biochemistry 22, 3581–3586 (1983).
Monteilhet, C. & Blow, D. M. J. molec. Biol. 22, 407–417 (1978).
Rubin, J. & Blow, D. M. J. molec. Biol. 145, 489–500 (1981).
Bhat, T. N., Blow, D. M., Brick, P. & Nyborg, J. J. molec. Biol. 158, 699–709 (1982).
Blow, D. M. & Brick, P. in Biological Macromolecules and Assemblies Vol. 2 (eds Jurnak, F. & McPherson, A.) 442–469 (Wiley, New York, 1985).
Fersht, A. R. et al. Angew. Chem. 23, 467–473 (1984).
Winter, G., Fersht, A. R., Wilkinson, A. J., Zoller, M. & Smith, M. Nature 299, 756–758 (1982).
Wilkinson, A. J., Fersht, A. R., Blow, D. M., Carter, P. & Winter, G. Nature 307, 187–188 (1984).
Fersht, A. Enzyme Structure and Mechanism Ch. 2 (Freeman, New York, 1985).
Carter, P. J., Winter, G., Wilkinson, A. J. & Fersht, A. R. Cell 38, 835–840 (1984).
Weiner, S. J. et al. J. Am. chem. Soc. 106, 765–784 (1984).
Jencks, W. P. Catalysis in Chemistry and Enzymology (McGraw-Hill, New York, 1969).
Hine, J. J. Am. chem. Soc. 94, 5766–5771 (1972).
Monteilhet, C., Blow, D. M. & Brick, P. J. molec. Biol. 173, 477–485 (1984).
Fersht, A. R. & Dingwall, C. Biochemistry 18, 1245–1249 (1979).
Fersht, A. R. Trends biochem. Sci. 9, 145–147 (1984).
Fersht, A. R. & Dingwall, C. Biochemistry 18, 2627–2631 (1979).
Waye, M. M. Y., Winter, G., Wilkinson, A. J. & Fersht, A. R. EMBO J. 2, 1827–1829 (1983).
Fersht, A. R., Shindler, J. S. & Tsui, W.-C. Biochemistry 19, 5520–5524 (1980).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Fersht, A., Shi, JP., Knill-Jones, J. et al. Hydrogen bonding and biological specificity analysed by protein engineering. Nature 314, 235–238 (1985). https://doi.org/10.1038/314235a0
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/314235a0