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Ribozyme catalysis: not different, just worse

Abstract

Evolution has resoundingly favored protein enzymes over RNA-based catalysts, yet ribozymes occupy important niches in modern cell biology that include the starring role in catalysis of protein synthesis on the ribosome. Recent results from structural and biochemical studies show that natural ribozymes use an impressive range of catalytic mechanisms, beyond metalloenzyme chemistry and analogous to more chemically diverse protein enzymes. These findings make it increasingly possible to compare details of RNA- and protein-based catalysis.

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Figure 1: Comparison of proposed mechanisms for RNA strand scission catalyzed by the protein enzyme RNase A and the HDV ribozyme.
Figure 2: Comparison of proposed mechanisms for hydrolysis of phosphodiesters catalyzed by 3′,5′-cyclic nucleotide phosphodiesterase 4 (PDE4) and the group I intron.
Figure 3: Possible mechanism for peptide bond formation catalyzed by the large subunit of the ribosome.

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Acknowledgements

The authors thank E. Friedman, K. Karbstein and A. Ke for helpful comments on the manuscript, R. Green and A. Mildvan for stimulating discussions, and A. Ke and S. Dorner for preparation of Figures 1b,d, 2b,d and 3b.

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Doudna, J., Lorsch, J. Ribozyme catalysis: not different, just worse. Nat Struct Mol Biol 12, 395–402 (2005). https://doi.org/10.1038/nsmb932

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