Disease relevance of ECs0029

• Initiator tRNA from yeast (tRNAMeti) was quantitatively misaminoacylated with L-isoleucine using isoleucyl-tRNA synthetase from Escherichia coli [1].
• We determined the crystal structures of the Thermus thermophilus IleRS CP1 domain alone, and in its complex with valine at 1.8- and 2.0-A resolutions, respectively [2].
• The methionyl-tRNA synthetases from Escherichia coli and Bacillus stearothermophilus and isoleucyl-tRNA synthetase from E. coli, for example, are shown to reject misactivated homocysteine rapidly by the pre-transfer route [3].

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

• By E. coli IleRS, E. coli tRNAIle was charged with furanomycin as efficiently as with L-isoleucine [7].
• In an attempt to elucidate the mechanism of the spermine effect on acylation and exchange, both reactions were re-examined using isoleucyl-tRNA synthetase from Escherichia coli [8].
• Measurement of the rate of activation of 5TFI by the E. coli isoleucyl-tRNA synthetase (IleRS) yielded a specificity constant (k(cat)/K(m)) 134-fold lower than that for isoleucine [9].
• Effect of inorganic pyrophosphate on the pretransfer proofreading in the isoleucyl-tRNA synthetase from Escherichia coli [10].
• The binding of 10 isomeric alpha-amino-heptanoic acids, of two isomeric alpha-amino-octanoic acids, of isoleucinol and valinol, and of various alpha-hydroxy acids to isoleucyl-tRNA synthetase from Escherichia coli MRE 600 has been investigated by an ultracentrifuge method [11].

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

• The conformation of IleRS-bound furanomycin was similar to that of L-isoleucine, although the chemical structure of furanomycin is unlike that of L-isoleucine [7].
• Correspondingly, some of the phosphate groups of these dispensable tertiary base-pair residues were shown to be exposed to N-nitroso-N-ethylurea when tRNA(Ile) was bound with IleRS [13].
• The IleRS-bound L-valine takes the gauche- form about the C alpha-C beta bond [16].
• The IleRS-bound L-isoleucine takes the gauche+ form about the C alpha-C beta bond and the trans form about the C beta-C gamma 1 bond [16].
• Both Co(2+)- and Cd(2+)-substituted IleRS were found to have kcat/Km values in the isoleucine-dependent ATP-pyrophosphate exchange assay approximately 5-fold lower than the native Zn2+ enzyme [17].

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].

References