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Gene Review

ileS  -  isoleucyl-tRNA synthetase

Escherichia coli O157:H7 str. Sakai

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Disease relevance of ECs0029


High impact information on ECs0029

  • Lysidine, a lysine-combined modified cytidine, is exclusively located at the anticodon wobble position (position 34) of eubacterial tRNA(Ile)(2) and not only converts the codon specificity from AUG to AUA, but also converts the aminoacylation specificity from recognition by methionyl-tRNA synthetase to that by isoleucyl-tRNA synthetase (IleRS) [4].
  • The cells harboring the P. fluorescens ileS were found to be most resistant to pseudomonic acid, while the transformants expressing the PS102 IleRS were more resistant than those containing the wild-type E. coli IleRS [5].
  • DNA sequence of the cloned ileS gene predicts that the P. fluorescens IleRS consists of 943 amino acids with 54% identity with the E. coli IleRS [5].
  • This mutational alteration in IleRS of an E. coli pseudomonic acid-resistant mutant resides in a region of the enzyme in close proximity to one of the consensus sequences of class I aminoacyl-tRNA synthetases, the KMSKS sequence between residues 602 and 606 of the E. coli IleRS [5].
  • The isoleucyl-tRNA synthetase (ileRS) gene [ilsA; formerly cupC, Martindale, D. W., Martindale, H. M., and Bruns, P. J. (1986) Nucleic Acids Res. 14, 1341-1354] from the ciliate Tetrahymena thermophila was sequenced and found to have eight introns, four transcription start sites, and a putative polypeptide of 1081 amino acids [6].

Chemical compound and disease context of ECs0029


Biological context of ECs0029

  • That these enzymatic reactions occur between Ile-tRNAIle or Ile-AMP (bound in the synthetic sub-site) and a thiol (an analogue of the side chain of homocysteine, bound in the editing sub-site), indicates that the two sub-sites are physically close on the surface of IleRS, forming a single synthetic/editing active site of the enzyme [12].
  • Thus, it is proposed that the recognition by IleRS of all the widely distributed identity determinants is coupled with a global conformational change that involves the loosening of a particular set of tertiary base-pairs of tRNA(Ile) [13].
  • The substrate specificity of isoleucyl-tRNA synthetase from Escherichia coli MRE 600 with regard to ATP analogs has been compared with the results obtained with isoleucyl-tRNA synthetase from yeast [14].
  • These results support the involvement of arginine residues in ATP binding with GS 2 or isoleucyl tRNA synthetase, and thus indicate that arginine residues of amino acid activating enzymes are essential for the formation of aminoacyl adenylates in both nonribosomal and ribosomal peptide biosynthesis [15].

Associations of ECs0029 with chemical compounds


Other interactions of ECs0029

  • A series of sulfamate surrogates of methionyl and isoleucyl adenylate have been investigated as MetRS and IleRS inhibitors by modifications of the sulfamate linker and adenine moieties [18].


  1. Isoleucyl initiator tRNA does not initiate eucaryotic protein synthesis. Wagner, T., Gross, M., Sigler, P.B. J. Biol. Chem. (1984) [Pubmed]
  2. Crystal structures of the CP1 domain from Thermus thermophilus isoleucyl-tRNA synthetase and its complex with L-valine. Fukunaga, R., Fukai, S., Ishitani, R., Nureki, O., Yokoyama, S. J. Biol. Chem. (2004) [Pubmed]
  3. Alternative pathways for editing non-cognate amino acids by aminoacyl-tRNA synthetases. Jakubowski, H., Fersht, A.R. Nucleic Acids Res. (1981) [Pubmed]
  4. Structural basis for lysidine formation by ATP pyrophosphatase accompanied by a lysine-specific loop and a tRNA-recognition domain. Nakanishi, K., Fukai, S., Ikeuchi, Y., Soma, A., Sekine, Y., Suzuki, T., Nureki, O. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  5. Relationship of protein structure of isoleucyl-tRNA synthetase with pseudomonic acid resistance of Escherichia coli. A proposed mode of action of pseudomonic acid as an inhibitor of isoleucyl-tRNA synthetase. Yanagisawa, T., Lee, J.T., Wu, H.C., Kawakami, M. J. Biol. Chem. (1994) [Pubmed]
  6. Isoleucyl-tRNA synthetase from the ciliated protozoan Tetrahymena thermophila. DNA sequence, gene regulation, and leucine zipper motifs. Csank, C., Martindale, D.W. J. Biol. Chem. (1992) [Pubmed]
  7. Nonprotein amino acid furanomycin, unlike isoleucine in chemical structure, is charged to isoleucine tRNA by isoleucyl-tRNA synthetase and incorporated into protein. Kohno, T., Kohda, D., Haruki, M., Yokoyama, S., Miyazawa, T. J. Biol. Chem. (1990) [Pubmed]
  8. The role of polyamines in the aminoacyl transfer ribonucleic acid synthetase reactions. Demonstration of the requirement for magnesium ion and a secondary stimulatory effect of spermine. Santi, D.V., Webster, R.W. J. Biol. Chem. (1975) [Pubmed]
  9. Incorporation of trifluoroisoleucine into proteins in vivo. Wang, P., Tang, Y., Tirrell, D.A. J. Am. Chem. Soc. (2003) [Pubmed]
  10. Effect of inorganic pyrophosphate on the pretransfer proofreading in the isoleucyl-tRNA synthetase from Escherichia coli. Airas, R.K. Eur. J. Biochem. (1992) [Pubmed]
  11. Influence of side-chain structure of aliphatic amino acids on binding to isoleucyl-tRNA synthetase from Escherichia coli MRE 600. Flossdorf, J., Prätorius, H.J., Kula, M.R. Eur. J. Biochem. (1976) [Pubmed]
  12. Proofreading in trans by an aminoacyl-tRNA synthetase: a model for single site editing by isoleucyl-tRNA synthetase. Jakubowski, H. Nucleic Acids Res. (1996) [Pubmed]
  13. Molecular recognition of the identity-determinant set of isoleucine transfer RNA from Escherichia coli. Nureki, O., Niimi, T., Muramatsu, T., Kanno, H., Kohno, T., Florentz, C., Giegé, R., Yokoyama, S. J. Mol. Biol. (1994) [Pubmed]
  14. Isoleucyl-tRNA synthetase from Escherichia coli MRE 600. Different pathways of the aminoacylation reaction depending on presence of pyrophosphatase, order of substrate addition in the pyrophosphate exchange, and substrate specificity with regard to ATP analogs. Freist, W., Sternbach, H., Cramer, F. Eur. J. Biochem. (1982) [Pubmed]
  15. A comparative study of essential arginine residues in Gramicidin S synthetase 2 and isoleucyl tRNA synthetase. Kanda, M., Hori, K., Miura, S., Yamada, Y., Saito, Y. J. Biochem. (1982) [Pubmed]
  16. NMR analyses of the conformations of L-isoleucine and L-valine bound to Escherichia coli isoleucyl-tRNA synthetase. Kohda, D., Kawai, G., Yokoyama, S., Kawakami, M., Mizushima, S., Miyazawa, T. Biochemistry (1987) [Pubmed]
  17. Probing the metal binding sites of Escherichia coli isoleucyl-tRNA synthetase. Xu, B., Trawick, B., Krudy, G.A., Phillips, R.M., Zhou, L., Rosevear, P.R. Biochemistry (1994) [Pubmed]
  18. N-Alkoxysulfamide, N-hydroxysulfamide, and sulfamate analogues of methionyl and isoleucyl adenylates as inhibitors of methionyl-tRNA and isoleucyl-tRNA synthetases. Lee, J., Kim, S.E., Lee, J.Y., Kim, S.Y., Kang, S.U., Seo, S.H., Chun, M.W., Kang, T., Choi, S.Y., Kim, H.O. Bioorg. Med. Chem. Lett. (2003) [Pubmed]
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