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Gene Review

MARS2  -  methionyl-tRNA synthetase 2, mitochondrial

Homo sapiens

Synonyms: MetRS, Methionine--tRNA ligase, mitochondrial, Methionyl-tRNA synthetase 2, Mitochondrial methionyl-tRNA synthetase, MtMetRS, ...
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Disease relevance of MARS2


High impact information on MARS2

  • The EMAPII-like domain contributed a 10-fold decrease in K:(M) for tRNA in the aminoacylation reaction catalyzed by the native enzyme, as compared with the C-terminally truncated MetRS [3].
  • Human mitochondrial methionyl-tRNA synthetase (human mtMetRS) has been identified from the human EST database [1].
  • In this study, potent lead compounds with a novel skeleton, including compound 27 with IC50 = 237 nM, were successfully identified as Escherichia coli MetRS inhibitors [4].
  • The preparation and structure-activity relationships (SARs) of potent and selective small molecule inhibitors of bacterial methionyl-tRNA synthetase (MetRS) derived from an oxazolone-dipeptide scaffold are described [2].
  • A post-translational pathway involves: 1) metabolic conversion of Hcy to thiolactone by methionyl-tRNAsynthetase (MetRS), and 2) acylation of protein lysine residues by Hcy thiolactone [5].

Biological context of MARS2

  • To address the effects of the modification of mtRNA on recognition of the mitochondrial tRNA by human mtMetRS, the kinetics of aminoacylation of native bovine mtRNA(Met) and of an in vitro transcript of the bovine mtRNA(Met) have also been investigated [1].
  • Additional activities involve MetRS in the maintenance of translational fidelity and in coordination of ribosome biogenesis with protein synthesis [6].
  • Contacts between MetRS and other proteins could be mediated not only by noncatalytic peptides but also by structural elements present in the catalytic core, e.g. Arg-Gly-Asp (RGD) motifs [6].
  • Methionyl-tRNA synthetase (MetRS) belongs to the family of 20 enzymes essential for protein biosynthesis [6].

Associations of MARS2 with chemical compounds

  • A translational pathway involves: 1) reversible S-nitrosylation of Hcy with nitric oxide produced by nitric oxide synthase; 2) aminoacylation of tRNAMet with S-nitroso-Hcy catalyzed by MetRS; and 3) transfer of S-nitroso-Hcy from S-nitroso-Hcy-tRNAMet into growing polypeptide chains at positions normally occupied by methionine [5].
  • By contrast, all patients had a significant rebound in bilirubin (+39%) 24 h following MARS-1; however, following MARS-2 a rebound was seen only in two cases (+220%) [7].


  1. Characterization of the human mitochondrial methionyl-tRNA synthetase. Spencer, A.C., Heck, A., Takeuchi, N., Watanabe, K., Spremulli, L.L. Biochemistry (2004) [Pubmed]
  2. Potent and selective inhibitors of bacterial methionyl tRNA synthetase derived from an oxazolone-dipeptide scaffold. Tandon, M., Coffen, D.L., Gallant, P., Keith, D., Ashwell, M.A. Bioorg. Med. Chem. Lett. (2004) [Pubmed]
  3. A recurrent general RNA binding domain appended to plant methionyl-tRNA synthetase acts as a cis-acting cofactor for aminoacylation. Kaminska, M., Deniziak, M., Kerjan, P., Barciszewski, J., Mirande, M. EMBO J. (2000) [Pubmed]
  4. Pharmacophore-based virtual screening: the discovery of novel methionyl-tRNA synthetase inhibitors. Kim, S.Y., Lee, Y.S., Kang, T., Kim, S., Lee, J. Bioorg. Med. Chem. Lett. (2006) [Pubmed]
  5. Protein N-homocysteinylation: implications for atherosclerosis. Jakubowski, H. Biomed. Pharmacother. (2001) [Pubmed]
  6. Methionyl-tRNA synthetase. Deniziak, M.A., Barciszewski, J. Acta Biochim. Pol. (2001) [Pubmed]
  7. Successful use of Molecular Absorbent Regenerating System (MARS) dialysis for the treatment of fulminant hepatic failure in children accidentally poisoned by toxic mushroom ingestion. Covic, A., Goldsmith, D.J., Gusbeth-Tatomir, P., Volovat, C., Dimitriu, A.G., Cristogel, F., Bizo, A. Liver Int. (2003) [Pubmed]
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