Substrate-assisted catalysis of peptide bond formation by the ribosome

Joshua S. Weinger, K. Mark Parnell, Silke Dorner, Rachel Green, Scott A. Strobel

Research output: Contribution to journalArticlepeer-review

228 Scopus citations


The ribosome accelerates the rate of peptide bond formation by at least 107-fold, but the catalytic mechanism remains controversial. Here we report evidence that a functional group on one of the tRNA substrates plays an essential catalytic role in the reaction. Substitution of the P-site tRNA A76 2′ OH with 2′ H or 2′ F results in at least a 10 6-fold reduction in the rate of peptide bond formation, but does not affect binding of the modified substrates. Such substrate-assisted catalysis is relatively uncommon among modern protein enzymes, but it is a property predicted to be essential for the evolution of enzymatic function. These results suggest that substrate assistance has been retained as a catalytic strategy during the evolution of the prebiotic peptidyl transferase center into the modern ribosome.

Original languageEnglish (US)
Pages (from-to)1101-1106
Number of pages6
JournalNature Structural and Molecular Biology
Issue number11
StatePublished - Nov 2004

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology


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