Abstract
Accurate prediction of electrostatic effects on catalytic activity is an essential component of protein design1–4. Site-directed mutagenesis of charged groups in subtilisin of Bacillus amyloliquefaciens has provided experimental measurements of electrostatic interactions which may be used to test such theoretical methods. The pKa of the histidine of the active site has been perturbed by +0.08 to –1.0 units by modifying one or two residues5–7. Electrostatic effects in proteins can be modelled by the algorithm of Warwicker and Watson, which uses classical electrostatics and considers both the charge position and the shape of the molecule8–10. Here we report that the algorithm can model several pKa shifts in subtilisin to fair accuracy.
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 Springer Link
- 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
1. Rogers, N. K. Prog. Biophys. molec. BioL 48, 37-66 (1986). 2. Tarn, S. C. & Williams, R. J. P. Struct. Bond. 63, 103-151 (1985). 3. Matthew, J. B. et al CRC crit. Rev. Biochem. 18, 91-197 (1985). 4. Warshel, A. & Russell, S. T. Q. Rev. Biophys. 17, 283-422 (1984). 5. Thomas, P. G., Russell, A. J. & Fersht, A. R. Nature 318, 375-376 (1985). 6. Russell, A. J., Thomas, P. G. & Fersht, A. R. /. molec. Biol. 193, 803-813 (1987). 7. Russell, A. J. & Fersht, A. R. Nature 328, 496-500 (1987). 8. Warwicker, J. & Watson, H. C. /. molec. BioL 157, 671-679 (1982). 9. Rogers, N. K. & Sternberg, M. J. E. /. molec. Biol. 174, 527-542 (1984). 10. Rogers, N. K., Moore, G. R. & Sternberg, M. J. E. /. molec. Biol 182, 613-616 (1985). 11. Hopfinger, A. J. in Conformational Properties of Macromolecules 59-63 (Academic, New York, 1973). 12. Mehler, E. L. & Eichele, G. Biochemistry 23, 3887-3891 (1984). 13. Jones, T. A. J. appL Crystallogr. 11, 268-272 (1978). 14. Tanford, C. & Roxby, R. Biochemistry 11, 2192-2198 (1972). 15. Gilson, M. K. & Honig, B. H. Nature 330, 84-86 (1987).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Sternberg, M., Hayes, F., Russell, A. et al. Prediction of electrostatic effects of engineering of protein charges. Nature 330, 86–88 (1987). https://doi.org/10.1038/330086a0
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/330086a0
This article is cited by
-
The pH stability of foot-and-mouth disease virus
Virology Journal (2017)
-
A review of protein engineering for the food industry
Molecular Biotechnology (1995)
-
Contribution of unusual Arginine-Arginine short-range interactions to stabilization and recognition in proteins
Journal of Protein Chemistry (1994)
-
Libraries of atomic multipole moments for precise modeling of electrostatic properties of amino acids
Amino Acids (1994)
Comments
By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.
