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Introduction to Mechanisms of Enzyme Catalysis01:13

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For many years, scientists thought that enzyme-substrate binding took place in a simple "lock-and-key" fashion. This model stated that the enzyme and substrate fit together perfectly in one instantaneous step. However, current research supports a more refined view scientists call induced fit. The induced-fit model expands upon the lock-and-key model by describing a more dynamic interaction between enzyme and substrate. As the enzyme and substrate come together, their interaction causes...
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The function of proteins depends on their native three-dimensional structure, which is dictated by the amino acid sequence of the specific protein. Folding of the polypeptide chain takes place under specific conditions that energetically favor the folded conformation. In contrast, protein denaturation occurs spontaneously under unfavorable conditions that disrupt the integrity of the folded conformation. Thus, the chemical and physical environment of a protein, such as significant changes in pH...
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The term ribozyme is used for RNA that can act as an enzyme. Ribozymes are mainly found in selected viruses, bacteria, plant organelles, and lower eukaryotes. Ribozymes were first discovered in 1982 when Tom Cech’s laboratory observed Group I introns acting as enzymes. This was shortly followed by the discovery of another ribozyme, Ribonulcease P, by Sid Altman’s laboratory. Both Cech and Altman received the Nobel Prize in chemistry in 1989 for their work on ribozymes.
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The hemoglobin in the blood, the chlorophyll in green plants, vitamin B-12, and the catalyst used in the manufacture of polyethylene all contain coordination compounds. Ions of the metals, especially the transition metals, are likely to form complexes.
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Polydentate ligands are most widely used in complexometric titrations because they form more stable complexes with the metal ions than mono- or bidentate ligands due to the chelate effect. Examples of polydentate ligands are ethylenediaminetetraacetic acid (EDTA), crown ethers, and cryptands. The most important feature of optimal polydentate ligands is the ability to form 1:1 complexes in a single-step process. Amino carboxylic acid derivatives are frequently used as complexing agents. EDTA is...
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Molecular Features and Metal Ions That Influence 10-23 DNAzyme Activity.

Hannah Rosenbach1, Julian Victor1, Manuel Etzkorn1,2

  • 1Institut für Physikalische Biologie, Heinrich-Heine-Universität Düsseldorf, Universitätsstraße 1, 40225 Duesseldorf, Germany.

Molecules (Basel, Switzerland)
|July 11, 2020
PubMed
Summary

Deoxyribozymes (DNAzymes) show promise for gene suppression therapies by cleaving specific RNA sequences. This review explores factors influencing their catalytic activity, aiding the development of improved DNAzyme applications.

Keywords:
RNA hydrolysiscatalysisdeoxyribozymes (DNAzymes)gene silencingmetal ion cofactors

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Area of Science:

  • Biochemistry
  • Molecular Biology
  • Therapeutic Applications

Background:

  • Deoxyribozymes (DNAzymes) possess RNA hydrolysis activity, enabling gene suppression for potential therapies.
  • The 10-23 DNAzyme, a well-studied example, binds and cleaves target RNA sequences between purine and pyrimidine nucleotides.
  • In vitro DNAzyme activity exceeds in vivo performance, potentially due to divalent cation dependency.

Purpose of the Study:

  • To review thermodynamic properties of DNAzymes.
  • To examine the impact of nucleobase modifications in the catalytic loop.
  • To elucidate the role of metal ions in DNAzyme catalysis.

Main Methods:

  • Literature review of existing biological studies on DNAzyme mechanisms.
  • Analysis of thermodynamic properties and nucleobase modifications.
  • Investigation into the role of various metal ions in catalysis.

Main Results:

  • Biological studies offer insights into deoxynucleotides and functional groups critical for DNAzyme activity.
  • Thermodynamic data and metal ion interactions are key factors influencing catalysis.
  • Nucleobase modifications can modulate catalytic efficiency.

Conclusions:

  • Understanding DNAzyme catalysis requires considering thermodynamic properties, nucleobase modifications, and metal ion roles.
  • These insights are crucial for developing novel strategies for structure determination.
  • Improved understanding will enhance DNAzyme activity in cellular environments, advancing therapeutic applications.