Jump to main content
Jump to site search
PLANNED MAINTENANCE Close the message box

Scheduled maintenance work on Tuesday 19th September 2017 from 8.00am to 4.00pm (BST).

During this time our website performance may be temporarily affected. If you have any questions please use the feedback button available under our menu button. We apologise for any inconvenience this might cause and thank you for your patience.



A water-mediated and substrate-assisted aminoacylation mechanism in the discriminating aminoacyl-tRNA synthetase GlnRS and non-discriminating GluRS

Author affiliations

Abstract

Glutaminyl-tRNA synthetase (GlnRS) catalyzes the aminoacylation of glutamine to the corresponding tRNAGln. However, most bacteria and all archaea lack GlnRS and thus an indirect noncanonical aminoacylation is required. With the assistance of a non-discriminating version of Glutamyl-tRNA synthetases (ND-GluRS) the tRNAGln is misaminoacylated by glutamate. In this study, we have computationally investigated the aminoacylation mechanism in GlnRS and ND-GluRS employing Molecular Dynamics (MD) simulations, Quantum Mechanics (QM) cluster and Quantum Mechanics/Molecular Mechanics (QM/MM) calculations. Our investigations demonstrated the feasibility of a water-mediated, substrate-assisted catalysis pathway with rate limiting steps occurring at energy barriers of 25.0 and 25.4 kcal mol−1 for GlnRS and ND-GluRS, respectively. A conserved lysine residue participates in a second proton transfer to facilitate the departure of the adenosine monophosphate (AMP) group. Thermodynamically stable (−29.9 and −9.3 kcal mol−1 for GlnRS and ND-GluRS) product complexes are obtained only when the AMP group is neutral.

Graphical abstract: A water-mediated and substrate-assisted aminoacylation mechanism in the discriminating aminoacyl-tRNA synthetase GlnRS and non-discriminating GluRS

Back to tab navigation

Supplementary files

Publication details

The article was received on 05 May 2017, accepted on 07 Sep 2017 and first published on 07 Sep 2017


Article type: Paper
DOI: 10.1039/C7CP02969A
Citation: Phys. Chem. Chem. Phys., 2017, Advance Article
  •   Request permissions

    A water-mediated and substrate-assisted aminoacylation mechanism in the discriminating aminoacyl-tRNA synthetase GlnRS and non-discriminating GluRS

    M. M. Aboelnga, J. J. Hayward and J. W. Gauld, Phys. Chem. Chem. Phys., 2017, Advance Article , DOI: 10.1039/C7CP02969A

Search articles by author

Spotlight

Advertisements