4EO4

Crystal structure of the yeast mitochondrial threonyl-tRNA synthetase (MST1) in complex with seryl sulfamoyl adenylate

Summary for 4EO4

• Entry DOI: 10.2210/pdb4eo4/pdb
• Related: 3UGQ 3UGT 3UH0
• Descriptor: Threonine--tRNA ligase, mitochondrial, 5'-O-(N-(L-SERYL)-SULFAMOYL)ADENOSINE, ZINC ION, ... (4 entities in total)
• Functional Keywords: aminoacyl-trna synthetase class ii, threonyl-trna synthetase, threonine trna, mitochondria, ligase
• Biological source: Saccharomyces cerevisiae (Baker's yeast)
• Cellular location: Mitochondrion matrix: P07236
• Total number of polymer chains: 4
• Total formula weight: 217624.38

Authors

Peterson, K.M.,Ling, J.,Simonovic, I.,Soll, D.,Simonovic, M. (deposition date: 2012-04-13, release date: 2012-07-11, Last modification date: 2024-02-28)

Primary citation

Ling, J.,Peterson, K.M.,Simonovic, I.,Soll, D.,Simonovic, M.
The mechanism of pre-transfer editing in yeast mitochondrial threonyl-tRNA synthetase.
J.Biol.Chem., 287:28518-28525, 2012

PubMed Abstract: Accurate translation of mRNA into protein is a fundamental biological process critical for maintaining normal cellular functions. To ensure translational fidelity, aminoacyl-tRNA synthetases (aaRSs) employ pre-transfer and post-transfer editing activities to hydrolyze misactivated and mischarged amino acids, respectively. Whereas post-transfer editing, which requires either a specialized domain in aaRS or a trans-protein factor, is well described, the mechanism of pre-transfer editing is less understood. Here, we show that yeast mitochondrial threonyl-tRNA synthetase (MST1), which lacks an editing domain, utilizes pre-transfer editing to discriminate against serine. MST1 misactivates serine and edits seryl adenylate (Ser-AMP) in a tRNA-independent manner. MST1 hydrolyzes 80% of misactivated Ser-AMP at a rate 4-fold higher than that for the cognate threonyl adenylate (Thr-AMP) while releasing 20% of Ser-AMP into the solution. To understand the mechanism of pre-transfer editing, we solved the crystal structure of MST1 complexed with an analog of Ser-AMP. The binding of the Ser-AMP analog to MST1 induces conformational changes in the aminoacylation active site, and it positions a potential hydrolytic water molecule more favorably for nucleophilic attack. In addition, inhibition results reveal that the Ser-AMP analog binds the active site 100-fold less tightly than the Thr-AMP analog. In conclusion, we propose that the plasticity of the aminoacylation site in MST1 allows binding of Ser-AMP and the appropriate positioning of the hydrolytic water molecule.

PubMed: 22773845
DOI: 10.1074/jbc.M112.372920

Experimental method

X-RAY DIFFRACTION (2.87 Å)