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Hammerhead ribozyme design and application
Cellular and Molecular Life Sciences CMLS, 1998The emerging knowledge about RNA-based enzymes has already had great impact on our concept of evolutionary history, making the 'RNA world' more likely. It may well have an equally important impact on the diagnostic and therapeutic practices of human and veterinary medicine in the next decade. We are not quite there yet. This review addresses the design
M Amarzguioui, H Prydz
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Thermodynamic Dissection of the Substrate−Ribozyme Interaction in the Hammerhead Ribozyme
Biochemistry, 1998The free energy of substrate binding to the hammerhead ribozyme was compared for 10 different hammerheads that differed in the length and sequence of their substrate recognition helices. These hammerheads were selected because neither ribozyme nor substrate oligonucleotide formed detectable alternate secondary structures.
Tracy K. Stage-Zimmermann +3 more
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The internal equilibrium of the hammerhead ribozyme reaction
Biochemistry, 1995The effects of temperature, pH, and magnesium ion concentration on the internal equilibrium of the hammerhead ribozyme reaction were determined in order to better understand why the ribozyme-bound substrate RNA is 99% cleaved at equilibrium. Cleavage of substrate is more efficient at higher temperatures because a large entropy gain upon cleavage ...
Olke C. Uhlenbeck, Klemens J. Hertel
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Hammerhead ribozymes for target validation
Expert Opinion on Therapeutic Targets, 2002Expensive failures in the pharmaceutical industry might be avoided by target validation at an early stage. Often, the full consequences of inhibiting a chosen drug target do not emerge until late in the development process. One option is to use hammerhead ribozymes as highly specific ribonucleases targeted exclusively at the mRNA encoding the target ...
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RNA Folding and Misfolding of the Hammerhead Ribozyme
Biochemistry, 1999The hammerhead ribozyme undergoes a well-defined two-stage folding process induced by the sequential binding of two magnesium ions. These probably correspond to the formation of domain 2 (0-500 microM magnesium ions) and domain 1 (1-20 mM magnesium ions), respectively.
Gurminder S. Bassi +3 more
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Probing general acid catalysis in the hammerhead ribozyme.
Journal of the American Chemical Society, 2008Recent crystallographic and computational studies have provided fresh insights into the catalytic mechanism of the RNA-cleaving hammerhead ribozyme. Based on these findings, specific ribozyme functional groups have been hypothesized to act directly as ...
Jason M. Thomas, D. Perrin
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Genomisch codierte Hammerhead-Ribozyme
BIOspektrum, 2012The hammerhead ribozyme is a small RNA motif capable to cleave RNA endonucleolytically. Originally discovered in sub-viral plant pathogens, recent studies have uncovered the presence of this ribozyme in an unprecedented number of bacterial and eukaryal genomes.
Christian Hammann +2 more
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Protein Enhancement of Hammerhead Ribozyme Catalysis
Science, 1993When the recognition sequence of a ribozyme is extended beyond a certain length, turnover is slowed and specificity is decreased. Here, it is shown that a protein can help a ribozyme overcome these general limitations on ribozyme activity. Cleavage of an RNA oligonucleotide by a hammerhead ribozyme is enhanced 10- to 20-fold upon addition of a protein ...
Mala Khosla +2 more
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Degradation of hammerhead ribozymes by human ribonucleases
Molecular and General Genetics MGG, 1998Hammerhead ribozymes were used as substrates to examine endoribonucleolytic activities in cell extracts and cultured human cells. Primer-extension analyses showed that ribozymes directed against tumor necrosis factor-alpha mRNA and human immunodeficiency virus type 1 tat mRNA were cleaved at UA and CA dinucleotides by extracts. Preferred cleavage sites
G. Kaplan +6 more
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A tale in molecular recognition: the hammerhead ribozyme
Journal of Molecular Recognition, 2006AbstractA new crystal structure of the hammerhead ribozyme demonstrates the influence of peripheral tertiary contacts on the local conformations around the active site. This structure resolves many conflicting results obtained on reduced systems. Copyright © 2006 John Wiley & Sons, Ltd.
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