title: Inhibition of the catalytic activity of trans-acting antigenomic delta ribozyme by selected antibiotics and their Cu2+ complexes.
abstract: 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.
authors.affiliation: Institute of Bioorganic Chemistry, Polish Academy of Sciences, Noskowskiego 12/14, 61-704 Poznań, Poland. wrzesinj@ibch.poznan.pl
authors.forename: Jan
authors.initials: J
authors.lastname: Wrzesinski
authors.forename: Magdalena
authors.initials: M
authors.lastname: Brzezowska
authors.forename: Wojciech
authors.initials: W
authors.lastname: Szczepanik
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Jezowska-Bojczuk
authors.forename: Jerzy
authors.initials: J
authors.lastname: Ciesiołka
mesh_terms: 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
chemical_list: D000900:Anti-Bacterial Agents; D016337:RNA, Catalytic; D003300:Copper