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Ribozymes02:47

Ribozymes

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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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Mechanistic models, a category encompassing both physiological and compartmental modeling, differ from empirical models' approaches to incorporating known factors about the systems being modeled. Empirical models describe data with minimal assumptions, while mechanistic models aim to provide a robust description of available data by specifying assumptions and integrating known factors about the system. Compartmental analysis is a key example of a mechanistic model in pharmacokinetics and...
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Isomerism in Complexes
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Mechanistic models are utilized in individual analysis using single-source data, but imperfections arise due to data collection errors, preventing perfect prediction of observed data. The mathematical equation involves known values (Xi), observed concentrations (Ci), measurement errors (εi), model parameters (ϕj), and the related function (ƒi) for i number of values. Different least-squares metrics quantify differences between predicted and observed values. The ordinary least...
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Production of Disulfide-stabilized Transmembrane Peptide Complexes for Structural Studies
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Structural Simplicity and Mechanistic Complexity in the Hammerhead Ribozyme.

Sara M O'Rourke1, William G Scott1

  • 1The Center for the Molecular Biology of RNA, University of California at Santa Cruz, Santa Cruz, CA, United States.

Progress in Molecular Biology and Translational Science
|October 21, 2018
PubMed
Summary
This summary is machine-generated.

Full-length hammerhead ribozymes are 1000x more active due to a single tertiary contact. This discovery simplifies understanding of ribozyme structure-activity relationships and challenges simple mechanistic models.

Keywords:
Acid-base catalysisFast minimal hammerheadHammerhead ribozyme catalysisHammerhead ribozyme structureTertiary contact

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Area of Science:

  • Biochemistry
  • Molecular Biology
  • RNA Catalysis

Background:

  • Hammerhead ribozymes are RNA enzymes crucial for various biological processes.
  • Full-length ribozymes exhibit significantly higher catalytic activity compared to minimal variants.
  • This enhanced activity is attributed to a complex tertiary interaction stabilizing the active site.

Purpose of the Study:

  • To investigate the structural basis for the enhanced activity of natural hammerhead ribozymes.
  • To determine the minimal structural requirements for hammerhead ribozyme catalytic efficiency.
  • To analyze alternative mechanistic interpretations in light of new structural data.

Main Methods:

  • Comparative analysis of full-length and minimal hammerhead ribozyme structures.
  • Biochemical assays to measure catalytic activity.
  • Structural biology techniques to elucidate tertiary interactions.

Main Results:

  • A single tertiary contact, an AU Hoogsteen pair between Stems I and II, accounts for the majority of the enhanced activity.
  • This interaction pre-organizes the active site for efficient acid-base catalysis.
  • The discovery simplifies the understanding of essential structural features for hammerhead ribozyme function.

Conclusions:

  • The AU Hoogsteen pair is a key determinant of hammerhead ribozyme catalytic efficiency.
  • Understanding this tertiary contact refines models of ribozyme mechanism and evolution.
  • Structural insights facilitate the design of more active ribozyme variants.