Catalytic tRNA

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Science  05 Nov 2004:
Vol. 306, Issue 5698, pp. 943
DOI: 10.1126/science.306.5698.943b

One of the central reactions in macromolecular biosynthesis is the formation of the peptide bond: the nucleophilic attack by the amino group (of the A-site amino acid that is added to the growing polypeptide) on the terminal carbonyl group of the growing polypeptide [which is attached via an ester linkage to the last base of the transfer RNA molecule (tRNA) that sits in the P site of the ribosome]. Structural analysis has revealed that there are no ribosomal proteins close enough to serve as chemical helpers for this reaction. Ribosomal RNA (rRNA), which is close enough, does not seem to help much either, according to mutagenesis results. On the other hand, recent work by Sievers et al. indicates that the ribosome may function as an entropy trap, accelerating the rate of reaction by a factor of 106 through careful positioning of the reactants and exclusion of water.

Weinger et al. have looked instead at the ribose portion of the last base (A76) in the P-site tRNA. By assessing the effects of replacing the 2' hydroxyl with a hydrogen or fluorine atom, they conclude that the nucleophilic attack is helped (also by a factor of 106) by what is, in essence, part of one of the reactants. They propose that this substrate-assisted reaction may be a holdover from the period when RNA carried out much of biochemistry, before protein enzymes evolved into expert catalysts. — GJC

Proc. Natl. Acad. Sci. U.S.A. 101, 7897 (2004); Nature Struct. Mol. Biol. 10.1038/nsmb841 (2004).

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