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Ribozymes are RNA molecules with catalytic activity (ribo- like ribonucleic acid, -zyme like enzyme). Despite having only four different chemical subunits (compare protein enzymes - 20 different amino acids) RNA molecules have amazing structural variety. They fold into complex tertiary structures analogous to highly structured proteins and catalyze a broad range of chemical reactions. RNA folding is a very hierarchical process -initially formed secondary structural elements undergo further folding into a three-dimensional complex that contains binding pockets for ligands or substrates and that provides catalytic centers for chemical reactions. Several ribozymes occur in nature, for example the hammerhead ribozyme, the hairpin ribozyme, the hepatitis delta virus ribozyme, and the neurospora VS ribozyme. These ribozymes are rather small and are derived from viruses, virusoides, viroids, and satellite RNA. Apart from these small ribo-zymes nature also harbors large RNA with catalytic properties, for example the self-splicing group I and group II RNA or the most prominent ribo-zyme, the ribosome. Although most naturally occurring ribozymes catalyze the cleavage or formation of phosphodiester bonds, peptide bond formation is catalyzed in the ribosome. Apart from this natural activity, ribozymes have been selected from large pools of RNA sequences to catalyze reactions such as aminoacylation, RNA polymerization, N-glycosidic bond-formation and cleavage, pyrophosphate bond-formation and cleavage, N-alkylation, S-alkylation, porphyrin metalation, biphenyl isomerization, and Diels-Alder and Michael reactions.

Fig. B.22.1. Catalytic cycle of a ribozyme. is formed and the substrate is cleaved at a

A suitable RNA substrate is bound to the specific position. Cleavage products ribozyme by Watson-Crick base pairing. dissociate from the ribozyme and the latter

On binding the catalytically active structure is free for the next round of catalysis.

Fig. B.22.1. Catalytic cycle of a ribozyme. is formed and the substrate is cleaved at a

A suitable RNA substrate is bound to the specific position. Cleavage products ribozyme by Watson-Crick base pairing. dissociate from the ribozyme and the latter

On binding the catalytically active structure is free for the next round of catalysis.

Ribozymes are paradigms of structure-function relationship, folding into a catalytically active structure is mirrored in activity. Most ribozymes behave like true catalysts; they have multiple turnover kinetics that can be described by the Michaelis-Menten model (Figure B.22.1).

The remarkable structural and functional versatility of RNA has prompted conjecture on the possibility of a life-form based primarily on RNA and preceding our DNA- and protein-based life. In this ''RNA world'' genetic information might have resided in the sequence of RNA molecules, with the phenotype being derived from the catalytic properties of RNA.

Further Reading

J. A. Doudna, T. R. Cech, Nature 2002, 418, 222-228.

A. JAschke, Curr. Opin. Struct. Biol. 2001, 11, 321-326.

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