Abstract
It is now possible to change at will amino acid residues in proteins by site-directed mutagenesis of their genes and hence perform structure-activity studies on molecular interactions. Residues in the tyrosyl-tRNA synthetase that are known from protein crystallographic studies to interact with the substrate are being systematically altered in this manner and the effects on binding and catalysis analysed. It is shown how the strengths of molecular interactions may be measured and how site-directed mutagenesis can probe such interactions. The results indicate how hydrogen bonding in enzyme-substrate complexes must be analysed in terms of an exchange process with solvent. This concept is used to predict a structural modification that increases the affinity of the enzyme for ATP. It is also seen how site-directed mutagenesis can provide evidence on theories of enzyme catalysis.
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© 1984 Pontificia Academia Scientiarum — Città del Vaticano
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Fersht, A.R., Winter, G. (1984). Studying Enzyme-Substrate Interactions by Site-Directed Mutagenesis. In: Chagas, C., Pullman, B. (eds) Specificity in Biological Interactions. Springer, Dordrecht. https://doi.org/10.1007/978-94-009-6457-0_7
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DOI: https://doi.org/10.1007/978-94-009-6457-0_7
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