Mechanistic studies of Hammerhead ribozytmes and their application in vivo
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The hammerhead ribozyme belongs to the class of molecules known as antisense RNAs.However, because of short extra sequences that form the so-called catalytic loop, it can act as an enzyme.Since the catalytic domain captures magnesium ions and magnesium ions can cleave phosphodiester bonds, hammerhead ribozymes are recognized as metalleozymes.In RNA cleaving reaction catalyzed by protein enzymes, the cleavage of phosphodiester bonds involves acid/base catalysis, with proton transfer occurring in the transition solvent isotope effects, in reaction catalyzed by hammerhead ribozymes, it became apparent that no proton transfer occurs in the transition state during reactions catalysed by a hammerhead ribozyme.This and an additional kinetic analysis, using a natural all-RNA substrate that contains a 5'-thio-leaving group at the cleavage site, revealed that hammerhead ribozymes exploit the general double-metal-ion mechanism of catalysis, with Mg2+ ions coordinating directly with the attacking and leaving oxygen moities.Since the hammerhead ribozyme is one of the smallest RNA enzymes known and has potential as a antiviral agent, thus ribozyme has been extensively investigated for application in vivo.Ribozymes are described that have possible utility as agents against HIV-1.
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Kazunari Taira, National Institute of Bioscence and Human Technology, Agency of Industrial Science and Technology, MTI Tsukuba Science City 305, Japan