Crystal structure of a hepatitis delta virus ribozyme

@article{FerrDAmar1998CrystalSO,
  title={Crystal structure of a hepatitis delta virus ribozyme},
  author={Adrian R. Ferr{\'e}-D’Amar{\'e} and Kaihong Zhou and Jennifer A. Doudna},
  journal={Nature},
  year={1998},
  volume={395},
  pages={567-574}
}
The self-cleaving ribozyme of the hepatitis delta virus (HDV) is the only catalytic RNA known to be required for the viability of a human pathogen. We obtained crystals of a 72-nucleotide, self-cleaved form of the genomic HDV ribozyme that diffract X-rays to 2.3 Å resolution by engineering the RNA to bind a small, basic protein without affecting ribozyme activity. The co-crystal structure shows that the compact catalytic core comprises five helical segments connected as an intricate nested… Expand
Catalytic strategies of the hepatitis delta virus ribozymes.
The hepatitis delta virus (HDV) ribozymes are self-cleaving RNA sequences critical to the replication of a small RNA genome. A recently determined crystal structure together with biochemical andExpand
Small self-cleaving ribozymes.
TLDR
The hammerhead, hairpin, hepatitis delta virus, Varkud Satellite, and glmS ribozymes catalyze sequence-specific intramolecular cleavage of RNA, which explains the abundance of riboz enzymes in contemporary organisms and supports a role for catalytic RNAs early in evolution. Expand
Ribozymes of the hepatitis delta virus: recent findings on their structure, mechanism of catalysis and possible applications.
TLDR
Details of the X-ray structure of the genomic delta ribozyme have greatly stimulated further studies on the folding of the ribozymes into functionally active molecules as well as on the mechanism of RNA catalysis. Expand
HDV family of self-cleaving ribozymes.
TLDR
Detailed analysis of additional HDV-like ribozyme isolates will likely reveal many more biological functions and provide information about the evolution of this unique RNA. Expand
Impact of an extruded nucleotide on cleavage activity and dynamic catalytic core conformation of the hepatitis delta virus ribozyme.
TLDR
Second-site mutagenesis experiments suggest that the identity of the nucleotide in position 76 (N76) indeed contributes to the catalytic activity of a trans-acting HDV ribozyme through its capacity for hydrogen bonding with P1. Expand
Disparate HDV ribozyme crystal structures represent intermediates on a rugged free-energy landscape.
TLDR
It is proposed that the available crystal structures of the HDV ribozyme represent intermediates on an overall rugged RNA folding free-energy landscape. Expand
A conformational switch controls hepatitis delta virus ribozyme catalysis
TLDR
Ten crystal structures of the HDV ribozyme in its pre-cleaved state are reported, showing that cytidine is positioned to activate the 2′-OH nucleophile in the precursor structure, which supports its proposed role as a general base in the reaction mechanism. Expand
Terbium-mediated footprinting probes a catalytic conformational switch in the antigenomic hepatitis delta virus ribozyme.
TLDR
It is demonstrated that a significant conformational change accompanies catalysis in the antigenomic HDV ribozyme in solution, similar to the catalytic conformational switch observed in crystals of the genomic form, and that structural and perhaps catalytic metal ions bind close to the catalysttic core. Expand
Transition State Features in the Hepatitis Delta Virus Ribozyme Reaction Revealed by Atomic Perturbations.
TLDR
The results delineate the functional relevance of atomic interactions inferred from structure, and suggest that the HDV ribozyme transition state resembles the cleavage product in the degree of proton transfer to the leaving group. Expand
delta virus ribozyme reveals key interactions of the L 3 loop Examination of the folding pathway of the antigenomic hepatitis
With the goal of gaining insight into the tertiary structure of the hepatitis delta virus ribozyme, cross-linking experiments using 4-thiouridine residues introduced in either the 59-end portion ofExpand
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TLDR
Data are consistent with a model in which the cleavage site is in close proximity to three single-stranded regions, consisting of a hairpin loop at the end of P3 and two sequences joining P1 to P4 and P4 to P2, which will aid in further mechanistic and structural studies of this RNA. Expand
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TLDR
A trans-acting system designed in order to explore the three-dimensional structure of the anti-genomic HDV ribozyme, it is demonstrated that RzANT is able to cleave specifically the RNA substrate as well as a deoxysubstrate analogue containing a single ribocytidine at the cleavage site (position -1). Expand
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TLDR
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