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Article
Nature Structural & Molecular Biology  11, 1101 - 1106 (2004)
Published online: 10 October 2004; | doi:10.1038/nsmb841

Substrate-assisted catalysis of peptide bond formation by the ribosome

Joshua S Weinger1, 3, K Mark Parnell1, 3, Silke Dorner2, Rachel Green2 & Scott A Strobel1

1  Department of Molecular Biophysics and Biochemistry, Yale University, 260 Whitney Avenue, New Haven, Connecticut 06520-8114, USA.

2  Department of Molecular Biology and Genetics, Johns Hopkins University Medical School, Howard Hughes Medical Institute, Baltimore, Maryland 21205, USA.

3  These authors contributed equally to this work.

Correspondence should be addressed to Scott A Strobel scott.strobel@csb.yale.edu
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 106-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.

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Nature Structural & Molecular Biology
ISSN: 1545-9993
EISSN: 1545-9985
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