Fidelity of seryl-tRNA synthetase to binding of natural amino acids from HierDock first principles computations

Protein Engineering, Design & Selection : PEDS
Christopher L McClendonWilliam A Goddard

Abstract

Seryl-tRNA synthetase (SerRS) charges serine to tRNA(Ser) following the formation of a seryl adenylate intermediate, but the extent to which other non-cognate amino acids compete with serine to bind to SerRS or for the formation of the activated seryl adenylate intermediate is not known. To examine the mechanism of discrimination against non-cognate amino acids, we calculated the relative binding energies of the 20 natural amino acids to SerRS. Starting with the crystal structure of SerRS from Thermus thermophilus with seryl adenylate bound, we used the HierDock and SCREAM (Side-Chain Rotamer Energy Analysis Method) computational methods to predict the binding conformation and binding energy of each of the 20 natural amino acids in the binding site in the best-binding mode and the activating mode. The ordering of the calculated binding energies in the activated mode agrees with kinetic measurements in yeast SerRS that threonine will compete with serine for formation of the activated intermediate while alanine and glycine will not compete significantly. In addition, we predict that asparagine will compete with serine for formation of the activated intermediate. Experiments to check the accuracy of this prediction would be useful...Continue Reading

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Citations

Aug 19, 2007·Journal of the American Chemical Society·Youyong LiAbdelazize Laoui
Oct 31, 2012·Biotechnology and Bioengineering·Lauren FeeneyMichael W Laird
Mar 21, 2015·The Journal of Physical Chemistry. B·Saheb Dutta, Nilashis Nandi
Jun 13, 2014·Current Opinion in Biotechnology·Robert P Harris, Peter M Kilby

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