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Dissociative Transition State in Hepatitis Delta Virus Ribozyme Catalysis
Benjamin Weissman1, Şölen Ekesan2, Hsuan-Chun Lin3
1Department of Chemistry and Department of Biochemistry and Molecular Biology, The University of Chicago, Chicago, Illinois 60637, United States.
Journal of the American Chemical Society
|January 27, 2023
Summary
Hepatitis delta virus ribozyme RNA cleavage proceeds via a dissociative, metaphosphate-like transition state. This differs from protein enzymes like ribonuclease A, indicating unique RNA enzyme active site designs.
Area of Science:
- Biochemistry
- Molecular Biology
- Enzymology
Background:
- Ribonucleases and ribozymes both cleave RNA via 2'-O-transphosphorylation.
- Understanding the transition states of these reactions is crucial for distinguishing protein and RNA enzyme mechanisms.
Purpose of the Study:
- To investigate the catalytic mechanism of the hepatitis delta virus ribozyme.
- To compare the transition state of ribozyme catalysis with that of protein enzymes and other RNA-cleaving agents.
Main Methods:
- Measurement of primary and secondary 18O kinetic isotope effects for hepatitis delta virus ribozyme.
- Analysis of transition state structures based on kinetic isotope effect data.
Main Results:
- The hepatitis delta virus ribozyme exhibits a dissociative, metaphosphate-like transition state.
- This transition state is distinct from the associative transition states observed for ribonuclease A and other catalytic systems.
Conclusions:
- The hepatitis delta virus ribozyme employs a unique active site design to achieve RNA cleavage.
- This distinct active site modulates the reaction pathway, leading to an altered transition state compared to protein enzymes.
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