Alternative pathways for editing non-cognate amino acids by aminoacyl-tRNA synthetases

Hieronim Jakubowski, Alan R.fersht

Research output: Contribution to journalArticlepeer-review

131 Scopus citations


Evidence is presented that the editing mechanisms of aminoacyl-tRNA synthetases operate by two alternative pathways: pre-transfer, by hydrolysis of the non-cognate aminoacyl adenylate; post-transfer, by hydrolysis of the mischarged tRNA. 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 pretransfer route. A novel feature of this reaction is that homocysteine thiolactone is formed by the facile cyclisation of the homocysteinyl adenylate. Valyl-tRNA synthetases, on the other hand, reject the more readily activated non-cognate amino acids by primarily the post-transfer route. The features governing the choice of pathway are discussed.

Original languageEnglish (US)
Pages (from-to)3105-3117
Number of pages13
JournalNucleic acids research
Issue number13
StatePublished - Jul 10 1981

All Science Journal Classification (ASJC) codes

  • Genetics

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