Lysyl-tRNA Synthetase Pre-Transfer Editing Mechanism

Submitter and Co-author information

Sameer Jafar, University of WindsorFollow

Type of Proposal

Visual Presentation (Poster, Installation, Demonstration)

Streaming Media

Faculty

Faculty of Science

Faculty Sponsor

Dr. J. W. Gauld

Start Date

24-3-2015 2:00 PM

End Date

24-3-2015 2:50 PM

Importance of the Project

Aminoacyl-tRNA synthetases are presumably very ancient enzymes that are thought to play key roles in a diverse range of physiological processes including viral assembly, inflammation, cell death, and protein synthesis. Specifically, they catalyze the covalent attachment of their respective amino acids to the corresponding cognate tRNAs (1). In addition to its obvious biological importance, a greater understanding of such processes could also lead to the development new catalysts or therapeutic agents.

(1) Martinis, S. A.; Boniecki, M. T., Febs Letters 2010, 584, 455-459.

Existing State of Knowledge

This process occurs via two half-reactions. In the first the amino acid is activated via reaction with ATP to give the aminoacyladenylate. The latter then is reacted with its cognate tRNA to give the desired aminoacyl-tRNA.

Research Question

Remarkably, despite their ancient nature, these enzymes are amongst some of the most accurate known. It is thought that they at least in part exploit pre- and post-transfer editing mechanisms to ensure no mis-acylation of the tRNA occurs. Unfortunately, how these mechanisms may occur is unknown.

Methodology

We have used a multi-scale computational chemistry approach to investigate possible mechanism(s) of pre-transfer editing in lysyl-tRNA synthetase (LysRS). Specifically, the mechanisms by which it transfers its native substrate lysyl and the non-cognate amino acid ornithine onto its cognate tRNA has been examined using docking, molecular dynamics and QM/MM methods. The complementary application of such computational methods provides insights that no single method, or experimental study can provide.

Your Findings

Some recent results and key findings from our studies will be presented.

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Mar 24th, 2:00 PM Mar 24th, 2:50 PM

Lysyl-tRNA Synthetase Pre-Transfer Editing Mechanism