YAKHAK HOEJI (약학회지)

The Pharmaceutical Society of Korea (대한약학회)
권호 표지

Screening of New Antibiotics Inhibiting Bacterial Methionyl-tRNA Synthetase

세균의 Methionyl-tRNA Synthetase를 저해하는 새로운 항생물질의 스크리닝

  • Published : 2001.06.01
Download PDF
⟨ Previous Next ⟩

Abstract

Aminoacyl tRNA synthetases of bacteria are known as potential targets for new anti-microbial agents. To isolate new inhibitors of bacterial methionyl-tRNA synthetases from natural sources, a new target-oriented screening system using whole cells which are over-expressing a target enzyme was developed. Approximately 8,000 culture broths of microorganisms from soils were tested by this screening system. Among them, ten culture broths was found to contain inhibitory activity against methionyl -tRNA synthetases of Escherichia coli. For the validation of the screening system, this new method was compared with in vitro enzymatic method. Seven out of 10 culture broths showed inhibitory activity against methionyl-tRNA synthetases of E. coli. This result showed that the new screening system was comparable to the enzyme assay. Thus we believe that our screening system as a new method can be applied for the screening of new antibiotics inhibiting bacterial methionyl-tRNA synthetases from natural products.

Keywords

References

  1. Science v.257 The crisis in antibiotic resistance Neu, H. C.
  2. FASEB J. v.12 Aminoacyl tRNA synthetases as targets for new anti-infectives Schimmel, P;Tao, J.;Hill, J.
  3. J. Bacteriol. v.160 Molecular cloning and primary structure of Escherichia coli methionyl-tRNA synthetase gene Dardel, F.;Fayat, G.;Blanquet, S.
  4. Bioorg. Med. Chem. Lett. v.9 Synthesis and structure-activity relationships of a series of novel thiazoles as inhibitors of aminoacyl-tRNA synthetases Yu, X. Y.;Hill, J. M.;Yu, G.;Wang, W.;Kluge, A. F.;Wendler, P.;Gallant, P.
  5. J. Mol. Biol. v.294 Crystal structure of Escherichia coli methionyl-tRNA synthetase highlights species-specific features Mechulam, Y.;Schmitt, E.;Maveyraud, L.;Zelwer, C.;Nureki, O.;Yokoyama, S.;Konno, M.;Blanquet, S.
  6. Eur. J. Biochem. v.179 Characterization of MSM1, the structural gene for yeast mitochondrial Methionyl-tRNA synthetase Tzagoloff, A.;Vambutas, A.;Akai, A.
  7. J. Mol. Biol. v.306 How methionyl-tRNA synthetase creates its amino acid recognition pocket upon L-methionine binding Serre, L.;Verdon, G.;Choinowski, T.;Hervouet, N.;Risler, J. L.;Zelwer, C.
  8. Clin. Pharm. v.6 Mupirocin;a topical antibiotic with a unique structure and mechanism of action Parenti, M. A.;Hatfield, S. M.;Leyden, J. J.
  9. Eur. j. Biochem. v.68 Indolmycin inhibits prokaryotic tryptophanyl-tRNA ligase Werner, R. G.;Thorpe, L. F.;Reuter, W.;Nierhaus, K. H.
  10. Bioorg. Med. Chem. Lett. v.9 Methionyl Adenylate Analogues as Inhibitors of Methioninyl-tRNA Synthetase Lee, J.;Kang, S. U.;Kang, M. K.;Chun, M. W.;Jo, Y. J.;Kwak, J. H.;Kim, S.
  11. Bioorg. Med. Chem. Lett. v.8 Methionine Analogues as Inhibitors of Methoninyl-tRNA Synthetase Lee, J.;Kang, M. K.;Chun, M. W.;Jo, Y. J.;Kwak, J. H.;Kim, S.
  12. NCCLS M2-A5 Performance Standards for Antimicrobial Disk Susceptibility tests-5th ed. National Committee for Clinical Laboratory Standards
  13. J. Mol. Biol. v.5 Identification of an amino acid region supporting specific methionyl-tRNA synthetase: tRNA recognition Mellot, P.;Mechulam, Y.;Corre, D. L.;Blanquet, S.;Fayat, G.