Nature Structural & Molecular Biology11, 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.
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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