Editing mechanism of aminoacyl-tRNA synthetases operates by a hybrid ribozyme/protein catalyst

Journal of the American Chemical Society
Yohsuke HagiwaraMasaru Tateno

Abstract

Aminoacyl-tRNA synthetases (aaRSs) are critical for the translational process, catalyzing the attachment of specific amino acids to their cognate tRNAs. To ensure formation of the correct aminoacyl-tRNA, and thereby enhance the reliability of translation, several aaRSs have an editing capability that hinders formation of misaminoacylated tRNAs. We investigated theoretically the mechanism of the editing reaction for a class I enzyme, leucyl-tRNA synthetase (LeuRS), complexed with a misaminoacylated tRNA(Leu), employing ab initio hybrid quantum mechanical/molecular mechanical potentials in conjunction with molecular dynamics simulations. It is shown that the water molecule that acts as the nucleophile in the editing reaction is activated by a 3'-hydroxyl group at the 3'-end of tRNA(Leu) and that the O2' atom of the leaving group of the substrate is capped by one of the water's hydrogen atoms. Thus, it is shown that editing is a self-cleavage reaction of the tRNA and so it is the tRNA, and not the protein, that drives the reaction. The protein does, however, have an important stabilizing effect on some high-energy intermediates along the reaction path, which is more efficient than the ribozyme would be alone. This indicates that e...Continue Reading

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Citations

Mar 31, 2012·The Journal of Physical Chemistry. B·Sandeep KumarKarin Musier-Forsyth
Jun 12, 2012·Nature Structural & Molecular Biology·Andrés PalenciaStephen Cusack
Nov 26, 2010·Proceedings of the National Academy of Sciences of the United States of America·Tanweer HussainRajan Sankaranarayanan
Dec 15, 2010·Proceedings of the National Academy of Sciences of the United States of America·Dino Moras
Apr 27, 2012·Journal of Biomedicine & Biotechnology·Jiyoung KangMasaru Tateno
Feb 18, 2016·Journal of Biomolecular Structure & Dynamics·Konstantin S BoyarshinMichael A Tukalo
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Mar 10, 2011·Journal of Physics. Condensed Matter : an Institute of Physics Journal·Yohsuke Hagiwara, Masaru Tateno
Jun 27, 2015·Nature Communications·Sadeem AhmadRajan Sankaranarayanan
Nov 8, 2017·Journal of Molecular Biology·Paul Kelly, Michael Ibba
Sep 20, 2011·The Journal of Physical Chemistry. B·Mauro Boero
Dec 28, 2017·The Journal of Physical Chemistry. B·Mohamed M AboelngaJames W Gauld

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