Proofreading in vivo: Editing of homocysteine by methionyl-tRNA synthetase in Escherichia coli

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Previous in vitro studies have established a pre-transfer proofreading mechanism for editing of homocysteine by bacterial methionyl-, isoleucyl-, and valyl-tRNA synthetases. The unusual feature of the editing is the formation of a distinct compound, homocysteine thiolactone. Now, two-dimensional TLC analysis of 35S-labeled amino acids extracted from cultures of the bacterium Escherichia coli reveals that the thiolactone is also synthesized in vivo. In E. coli, the thiolactone is made from homocysteine in a reaction catalyzed by methionyl-tRNA synthetase. One molecule of homocysteine is edited as thiolactone per 109 molecules of methionine incorporated into protein in vivo. These results not only directly demonstrate that the adenylate proofreading pathway for rejection of misactivated homocysteine operates in vivo in E. coli but, in general, establish the importance of error-editing mechanisms in living cells.

Original languageEnglish (US)
Pages (from-to)4504-4508
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number12
StatePublished - 1990

All Science Journal Classification (ASJC) codes

  • General


  • aminoacyl adenylate
  • homocysteine thiolactone
  • in vivo S-labeling
  • methionine biosynthesis
  • translational accuracy

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