Ribozyme ribonuclease

However, there are a number of other miscellaneous biological roles played by this complex. The [Co(NH3)6]3+ ion has been shown to inhibit the hammerhead ribozyme by displacing a Mn2+ ion from the active site.576 However, [Co(NH3)6]3+ does not inhibit ribonuclease H (RNase),577 topoisomerase I,578 or hairpin ribozyme,579 which require activation by Mg2+ ions. The conclusions from these studies were that an outer sphere complex formation between the enzyme and Mgaq2+ is occuring rather than specific coordination of the divalent ion to the protein. These results are in contrast to DNase I inhibition by the same hexaammine complex. Inhibition of glucose-induced insulin secretion from pancreatic cells by [Co(NH3)6]3+ has been found.580 Intracellular injection of [Co(NH3)6]3+ into a neurone has been found to cause characteristic changes to the structure of its mitochondria, and this offers a simple technique to label neuronal profiles for examination of their ultrastructures.581... 

In many enzymes, the value of kc-JK lies between 108 and 109 M s. The value for L 19 RNA is 103 M 1 s1, i.e., five orders of magnitude lower than for protein enzymes with high catalytic activity. However, L 19 RNA does compare in its efficiency to the enzyme ribonuclease A. The capabilities of ribozymes referred to above dealt solely with interactions of RNA (i.e., ribozymes) with RNA molecules. In a (hypothetical) RNA world, they would, however, need to be capable of doing much more, e.g., carrying out reactions at the carbon skeletons of biomolecules. 

Fig. 4A The mechanism of cleavage by ribonuclease A. Two imidazole residues function as general acid-base catalysts. B The single-metal-ion mechanism proposed for cleavage by the hammerhead ribozyme. One metal ion binds directly to the pro-Rp oxygen and functions as a general base catalyst. C The double-metal-ion mechanism proposed for cleavage by the hammerhead ribozyme. Two metal ions bind directly to the 2 -oxygen and the 5 -oxygen...

Frank, D.N. Pace, N.R. (1998) Ribonuclease P unity and diversity in a tRNA-processing ribozyme. Annu. Rev. Biochem. 

Self-splicing KNA. The precursor to the 26S rRNA of Tetrahymena contains a 413-nucleotide intron, which was shown by Cedi and coworkers to be selfsplicing, i.e., not to require a protein catalyst for maturation.581 582 This pre-rRNA is a ribozyme with true catalytic properties (Chapter 12). It folds into a complex three-dimensional structure which provides a binding site for free guanosine whose 3-OH attacks the phosphorus at the 5 end of the intron as shown in Fig. 28-18A, step a. The reaction is a simple displacement on phosphorus, a transesterification similar to that in the first step of pancreatic ribonuclease action (Eq. 12-25). The resulting free 3-OH then attacks the phosphorus atom at the other end of the intron (step b) to accomplish the splicing and to release the intron as a linear polynucleotide. The excised intron undergoes... 

Pieken, W.A., Olsen, D.B., Benseler, F., Aurup, H. and Eckstein, F. (1991) Kinetic characterization of ribonuclease-resistant 2 -modified hammerhead ribozymes. Science, 253, 314-317. 

Subsequently, several other kinds of ribozymes were discovered ribonuclease P, which cleaves transfer RNA precursors another variety of intron from fungi, which carries out its own removal a number of viral RNAs, which cleave themselves from large end-to-end intermediates to give genomic-sized RNAs and, most remarkably, the ribosome. Originally, all of these RNAs were thought to have a similar mechanism however, this may be an oversimplification, and more RNA-catalyzed reactions may exist (perhaps in the spliceo-some) waiting to be characterized. 

In most cases, proteins called enzymes (or abzymes-see here) catalyze chemical reactions. It turns out, however, that some RNA molecules, called ribozymes are capable of catalyzing chemical reactions too. Figure 11.29 shows the site of action of the RNA-protein complex called ribonuclease P. The RNA portion of the complex can, by itself, catalyze the hydrolysis of the specific bond indicated by the red wedge in the figure. 

---