Aminoglycosides ribozymes

Aminoglycoside binding to RNA is not limited to binding to prokaryotic 165 ribo-somal RNA. These positively charged molecules interact with the HlV-1 Rev Response Element (RRE) transcriptional activator region [17] and TAR RNA [151], interfere with intron splicing [146], and bind to hammerhead ribozymes [153]. 

The hammerhead ribozyme is a small RNA that catalyzes specific RNA cleavage in the sugar-phosphate backbone. The function of this RNA strongly relies on Mg placement to maintain structural integrity. Aminoglycoside action in inhibition of hammerhead ribozyme function has been shown to involve displacement of these necessary Mg ions. Structural studies of the hammerhead ribozyme bound by neomycin have indicated that the charged ammo-... 

Aminoglycosides are also known to inhibit group I intron splicing. Footprinting studies have indicated that neomycin, as it does with other ribozymes, most probably displaces metal ions to elicit its action in inhibiting splicing. Detailed mutational studies, coupled with molecular modeling, have shown that displacement of two Mg ions is required for inhibition. ... 

A more recently discovered ribozyme that binds neomycin, RNase P is responsible for the maturation at the 5 end of all tRNA in both prokaryotes and eukaryotes. Bacterial RNase P consists of a small RNA and protein subunit, of which the RNA acts as the catalyst in the cleavage reaction. Like the group 1 intron ribozyme, inhibition of activity by such aminoglycosides as neomycin is suggested to occur as a result of the displacement of two important Mg ... 

T. Hermann and E. Westhof, Aminoglycoside binding to the hammerhead ribozyme a general model for the interaction of cationic antibiotics with RNA, J. Mol Biol, 276 (1998) 903-912. 

Y. Tor, T. Hermann, and E. Westhof, Deciphering RNA recognition aminoglycoside binding to the hammerhead ribozyme, Chem. Biol, 5 (1998) R277-R283. 

D. J. Earnshaw and M. J. Gait, Hairpin ribozyme cleavage catalyzed by aminoglycoside antibiotics and the polyamine spermine in the absence of metal ions, Nucleic Acids Res., 26 (1998) 5551-5561. 

Drugs/toxins Ricin (toxin) from castor oil beans (Ricinus communis) is a ribonuclease that inhibits protein synthesis by cleaving and thus inactivating 28S rRNA. A single molecule of ricin within a cell attacks all the ribosomes and kiUs the ceU Diphtheria toxin an exotoxin secreted by Corynebacterium diphtheriae that inactivates eukaryotic elongation factor 2. A single molecule can kill a ceU Aminoglycosides prevent the formation of the initiation complex Tetracyclines bind to the A site and block the attachment of aminoacyl-tRNA Chloramphenicol inhibits peptidyl transferase (ribozyme) Macrolides and clindamycin bind to the SOS subunit and block translocation... 

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