Nucleic acid catalysis

Polymerization of nucleotides is an imperative for the story to come off. Clearly, catalysis by proteinaceous enzymes is a higher level complexity that had to await completion of the nucleic acid polymers. The recent discovery of nucleic acid catalysis has built a bridge between the nucleic acid and the protein world8 and simultaneously cracked open the door to the multiple origin world. Nucleic acid catalysts were not as versatile and efficient as proteineaceous ones, but catalysts nonetheless. 

Beyond generating novel species for the study of molecular recognition and nucleic acid catalysis, these experiments can provide fundamental insights into the nature of the landscapes that govern molecular evolution. By analyzing the relationships between selected sequences and their attendant functions, we can better understand how difficult it may be to chance upon function, and what the probable course of evolution may be once a nascent function has been discovered. 

Recall State why the following terms are important in biochemistry polymer, protein, nucleic acid, catalysis, genetic code. 

En me Mechanism. Staphylococcal nuclease (SNase) accelerates the hydrolysis of phosphodiester bonds in nucleic acids (qv) some 10 -fold over the uncatalyzed rate (r93 and references therein). Mutagenesis studies in which Glu43 has been replaced by Asp or Gin have shown Glu to be important for high catalytic activity. The enzyme mechanism is thought to involve base catalysis in which Glu43 acts as a general base and activates a water molecule that attacks the phosphodiester backbone of DNA. To study this mechanistic possibiUty further, Glu was replaced by two unnatural amino acids. 

By the end of this chapter, we will have seen all the common functional groups. Of those groups, amines and carbonyl compounds are the most abundant and have the richest chemistry. In addition to the proteins and nucleic acids already mentioned, the majority of pharmaceutical agents contain amine functional groups, and many of the common coenzymes necessary for biological catalysis are amines. 

The hypothesis that our biological world built on the DNA-RNA-protein central dogma was preceded by an RNA world in which RNA molecules carried both the genetic information and executed the gene functions (through ribozyme activity) is now widely accepted [130]. However, it is also well recognized that RNA due to its vulnerability to hydrolysis - especially as a result of catalysis by divalent metal ions - would not have been able to evolve in a harsh pre-biotic environment Also the formation of RNA under presumed pre-biotic conditions is extremely inefficient It is not so far-fetched to propose that a peptide nucleic acid-like molecule may have been able to function as a form of pre-biotic genetic material since it... 

Wang, W. et al., Biomolecular simulations recent developments in force fields, simulations of enzyme catalysis, protein-ligand, protein-protein, and protein-nucleic acid noncovalent interactions, Annu. Rev. Biophys. Biomol. Struct. 2001, 30, 211-243... 

Abstract This chapter updates but mostly supplements the author s Ange-wandte Review,111 setting in context recent advances based on protein and nucleic acid engineering. Systems qualify as a true enzyme mimics if there is experimental evidence for both the initial binding interaction and catalysis with turnover, generally in the shape of saturation kinetics. They are discussed under five broad headings mimics based on natural enzymes, on other proteins, on other biopolymers, on synthetic macromolecules and on small-molecule host-guest interactions. 

Nucleic acid stabilization, electrostatics, structure and potential stabilization or catalysis in enzymes... 

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