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Hydrogen bonding and biological specificity analysed by protein engineering

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.

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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

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