Inhibition of the catalytic activity of trans-acting antigenomic delta ribozyme by selected antibiotics and their Cu2+ complexes.
The effect of selected 10 antibiotics and their complexes with Cu(2+) ions on the catalytic activity of the trans-acting antigenomic delta ribozyme was investigated. Sisomicin, vancomycin, and actinomycin D displayed weak inhibitory properties. However, much stronger effects were detected with complexes of these antibiotics with Cu(2+) ions. The strongest inhibition was observed with actinomycin D-Cu(2+) complex, for which the calculated K(i) value was reduced ca. 35-fold upon metal ion complexation. We postulate that the antibiotic-Cu(2+) complexes are guided to the ribozyme metal ion binding site(s) presumably displacing the catalytically important metal ion(s). Moreover, we assume that, once positioned in appropriate distances to RNA phosphate groups and bases, the coordinated Cu(2+) ions become positively charged factors that enhance the affinity of the antibiotics to the ribozyme. These observations indicate that coordination of metal ions to antibiotics substantially changes their properties which might also have a biological relevance inside the cell.
Wrzesinski
Jan
J
Institute of Bioorganic Chemistry, Polish Academy of Sciences, Noskowskiego 12/14, 61-704 Poznań, Poland. wrzesinj@ibch.poznan.pl
Brzezowska
Magdalena
M
Szczepanik
Wojciech
W
Jezowska-Bojczuk
Małgorzata
M
Ciesiołka
Jerzy
J
D000900:Anti-Bacterial Agents / Q000737:chemistry*; D002384:Catalysis; D003300:Copper / Q000737:chemistry*; D004789:Enzyme Activation; D016678:Genome / Q000235:genetics; D016337:RNA, Catalytic / Q000737:chemistry* / Q000235:genetics; D015533:Transcriptional Activation / Q000235:genetics
D000900:Anti-Bacterial Agents; D016337:RNA, Catalytic; D003300:Copper