Catalytic RNA and DNA

All enzymes are proteins The term enzymes refers to biological catalysts, which are proteins with molecular weights generally ranging from 1.5 x 104 to 10s daltons. The nonprotein biocatalysts such as catalytic RNA and DNA are known as ribozymes (Doherty and Doudna, 2000 Scott and Klug, 1996)... 

Nevinsky GA, Buneva VN. 2002. Human catalytic RNA- and DNA-hydrolyzing antibodies. J Immunol Methods 269 235-249. 

Chapter 6 discussed Group II metal ions in biomolecules, concentrating on magnesium ions in catalytic RNA and on two calcium-containing biomolecules calmodulin and Ca -ATPase. Readers interested in the evolutionary aspects of catalytic RNA as a precursor to the DNA-based life forms that exist in the present time could begin by consulting the publications fisted in... 

The more successful strategy for the isolation of RNA- and DNA-based catalysts involves the direct screening of nucleic acids libraries for catalytic activity. This approach is called direct selection [6, 65, 77, 78, 86, 101-107]. In direct selections, nucleic acids that are capable of catalyzing a particular chemical transformation modify themselves with a tag or other characteristic that allows their preferential enrichment over those molecules which are catalytically inactive [108]. The design of ribozyme-selections involving reactions between two small substrates requires that one reactant be covalently attached to every individual member of the starting RNA pool. After the reaction with another substrate which usually carries the selection-tag has occurred, the self-modified RNA is immobilized on a solid support, separated from non-active molecules, and then cleaved off the support. 

The existence of catalytic RNAs and pathways for the interconversion of RNA and DNA has led to speculation that an important stage in evolution was the appearance of an RNA... 

We shall now briefly outline some of the features of the zinc metalloenzymes which have attracted most research effort several reviews are available, these are indicated under the particular enzyme, and for more detailed information the reader is referred to these. Attention is focussed here, albeit briefly, on carbonic anhydrases,1241,1262,1268 carboxypeptidases, leucine amino peptidase,1241,1262 alkaline phosphatases and the RNA and DNA polymerases.1241,1262,1462 Finally, we examine alcohol dehydrogenases in rather more detail to illustrate the use of the many elegant techniques now available. These enzymes have also attracted much effort from modellers of the enzymic reaction and such studies, which reveal much interesting coordination chemistry and often new catalytic properties in their own right—and often little about the enzyme system itself (except to indicate possibilities), will be mentioned in the next section of this chapter. 

The existence of catalytic RNAs and pathways for the interconversion of RNA and DNA has led to speculation that an important stage in evolution was the appearance of an RNA (or an equivalent polymer) that could catalyze its own replication. The biochemical potential of RNAs can be explored by SELEX, a method for rapidly selecting RNA sequences with particular binding or catalytic properties. 

One striking observation about the reactions catalyzed by RTA and pertussis toxin is that the enzymes appear to use opposite catalytic strategies. The analogous non-enzymatic reactions, hydrolysis of adenosine 5 -monophosphate (AMP) and NAD, both have highly dissociative AnD mechanisms with oxocarbenium ionlike transition states. In the ADP-ribosylation of protein Gid by pertussis toxin, the AnDn mechanism is more synchronous, with more nucleophile participation and lower oxocarbenium ion character than the non-enzymatic reaction. " In contrast, the RTA-catalyzed depurination of RNA" and DNA substrates proceeds through stepwise Dj,j An mechanisms where the enzyme stabilizes an oxocarbenium ion to the point that it becomes a discrete intermediate. This is illustrated with a hypothetical free energy surface for each reaction (Fig. 14). 

Nevirapine is a dipyridodiazepinone derivative that binds directly to RT. Thus, it blocks RNA- and DNA-dependent polymerase activities by causing a disruption of the enzyme s catalytic site. The activity of nevirapine does not compete with template or nucleoside triphosphate. The HIV-2 RT and human DNA polymerases are not inhibited by nevirapine. The 50% inhibitory concentration ranged within 10 to 100 nM against HIV-1. 

Nucleic acids Ribozymes (catalytic RNA) and deoxyribozymes (catalytic DNA)... 

This paper describes the development and initial applications of nab, a computer language for modeling biological macromolecules. It was developed to create atomic-level models of nucleic acid structures such as stem-loops, pseudoknots, multi-armed junctions and catalytic RNAs, and to investigate biological processes that involve nucleic acids, such as hybridization, branch migration at junctions, and DNA replication. 

Typical tertiary interactions of RNA include base triplets, H-bonds between base and sugar OH group, and between base and phosphate. As yet, tRNAs are the most abundant sources for the detailed 3-D structural information of RNA. Nevertheless, tertiary structures play an essential role in various catalytic functions of RNA whose expanding repertoire includes endonuclease/ligase (i.e., cleavage and ligation reactions of phosphodiester or phosphomonoester bonds in RNA and DNA), carbonyl esterase, and peptidyltransferase. 

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