Nature 314, 235 - 238 (21 March 1985); doi:10.1038/314235a0

Hydrogen bonding and biological specificity analysed by protein engineering

Alan R. Fersht^*, Jian-Ping Shi^*, Jack Knill-Jones^*, Denise M. Lowe^*, Anthony J. Wilkinson^*, David M. Blow^†, Peter Brick^†, Paul Carter^‡, Mary M. Y. Waye^‡ & Greg Winter^‡

^*Departments of Chemistry and ^†Physics, Imperial College of Science and Technology, London SW7 2AY, UK
^‡MRC Laboratory of Molecular Biology, MRC Centre, Hills Road, Cambridge CB2 2QH, UK

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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