Three-dimensional structure of a hammerhead ribozyme

  title={Three-dimensional structure of a hammerhead ribozyme},
  author={Heinz W. Pley and Kevin M. Flaherty and David B. Mckay},
The hammerhead ribozyme is a small catalytic RNA motif made up of three base-paired stems and a core of highly conserved, non-complementary nucleotides essential for catalysis. The X-ray crystallographic structure of a hammerhead RNA–DNA ribozyme-inhibitor complex at 2.6 Å resolution reveals that the base-paired stems are A-form helices and that the core has two structural domains. The first domain is formed by the sequence 5′-CUGA following stem I and is a sharp turn identical to the uridine… 
Molecular dynamics investigations of hammerhead ribozyme RNA
Molecular dynamics simulations of the solvated crystal structure of an active hammerhead ribozyme, obtained after flash-freezing crystals soaked with magnesium, demonstrate that molecular dynamics simulations can be successfully used to investigate the dynamical behaviour of a ribo enzyme.
Hammerhead ribozyme kinetics.
The X-ray crystal structures of two hammerhead ribozyme–inhibitor complexes revealed that the core residues fold into two separate domains and the helices are arranged in a Y-shape conformation.
The Varkud satellite ribozyme.
The VS ribozyme is the largest nucleolytic ribo enzyme, for which there is no crystal structure to date, and A756, a particularly critical nucleotide, is a strong candidate for nucleobase participation in the catalytic chemistry.
Three-Dimensional Structure of the Hammerhead Ribozyme
It has been demonstrated that short, synthetic oligoribonucleotides in which the consensus core is maintained but any or all of the stems are left openended can catalyze multiple-turnover cleavage in trans, and thus the hammerhead motif can act as a classical enzyme.
Crystal structure and mechanistic investigation of the twister ribozyme.
Mechanistic evidence supports a role for this guanine as either a general base or acid in a concerted, general acid-base-catalyzed cleavage reaction in the recently described nucleolytic ribozyme twister.
NMR solution structure of the lead-dependent ribozyme: evidence for dynamics in RNA catalysis.
A model for metal-binding in the leadzyme is proposed in which a lead ion binds to a bulged guanine base that is critical for leadzyme function.
The hammerhead ribozyme: structure, catalysis, and gene regulation.
Probing the Cleavage Activity of the Hammerhead Ribozyme Using Analog Complexes
The hammerhead ribozyme is a relatively small RNA catalyst that is derived from a structural motif present in the RNA genomes of several plant pathogens, where it is believed that RNA-mediated cleavage events are an essential step in the viroid’s replication pathway.


Sequence requirements of the hammerhead RNA self-cleavage reaction.
The refined consensus hammerhead resulting from this work was used to identify potential hammerheads present in a variety of Escherichia coli gene sequences, suggesting that the hammerhead contains few, if any, replaceable tertiary interactions as are found in tRNA.
Mixed deoxyribo- and ribo-oligonucleotides with catalytic activity
Structurally less-disrupted hammerhead analogues in which deoxyribon nucleotides, which lack 2′-OH groups, are substituted for ribonucleotides are constructed, indicating that the three-dimensional struc-ture producing nucleic acid-type catalysis is not restricted to RNA.
Hammerhead ribozymes: importance of stem-loop II for activity.
  • T. Tuschl, F. Eckstein
  • Chemistry
    Proceedings of the National Academy of Sciences of the United States of America
  • 1993
The activity of several hammerhead ribozyme constructs with constant lengths of stems I and III of 5 nt each but with variously shortened stems II is reported, and the structural requirement for optimal activity in these constructs where the chemical-cleavage step is rate limiting is determined by the stabilization of the transition state.
Mutagenesis analysis of a self-cleaving RNA.
There is flexibility in the sequence requirements for self-cleavage in vitro, but alterations of the conserved sequence or predicted secondary structure generally reduced the efficiency of self- Cleavage.
Thiophosphate interference experiments locate phosphates important for the hammerhead RNA self-cleavage reaction.
A phosphorothioate substitution interference assay is used to identify four phosphates in the conserved core which also play a role in the self-cleavage reaction.
Crystals of a hammerhead ribozyme.
The role of the exocyclic amino groups of conserved purines in hammerhead ribozyme cleavage.
  • G. Slim, M. Gait
  • Biology, Chemistry
    Biochemical and biophysical research communications
  • 1992
A kinetic and thermodynamic framework for the hammerhead ribozyme reaction.
A hammerhead ribozyme with eight potential base pairs in each of the substrate recognition helices stabilized product binding sufficiently to enable investigation of the ligation of oligonucleotides bound to the ribo enzymes, providing a basis for future mechanistic studies.
Structural domains of transfer RNA molecules.
Various detailed features of the conformation of yeast tRNA(Phe) revealed by recent refinement analysis of x-ray diffraction data at 2.5 A resolution are described.