{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2024,7,3]],"date-time":"2024-07-03T23:11:28Z","timestamp":1720048288108},"reference-count":50,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2013,4,18]],"date-time":"2013-04-18T00:00:00Z","timestamp":1366243200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["febs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FEBS Journal"],"published-print":{"date-parts":[[2013,6]]},"abstract":"<jats:p>The interactions of selected antibiotics with the <jats:italic>trans<\/jats:italic>\u2010acting antigenomic delta ribozyme were mapped. Ribozyme with two oligonucleotide substrates was used, one uncleavable with deoxycytidine at the cleavage site, mimicking the initial state of ribozyme, and the other with an all\u2010<jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content> substrate mimicking, after cleavage, the product state. Mapping was performed with a set of <jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content> structural probing methods: <jats:styled-content style=\"fixed-case\">P<\/jats:styled-content>b<jats:sup>2+<\/jats:sup> \u2010induced cleavage, nuclease digestion, and the selective 2\u2032\u2010hydroxyl acylation analyzed by primer extension (<jats:styled-content style=\"fixed-case\">SHAPE<\/jats:styled-content>) approach. The experimental results combined with molecular modeling revealed different binding sites for neomycin\u00a0<jats:styled-content style=\"fixed-case\">B<\/jats:styled-content>, amikacin and actinomycin\u00a0<jats:styled-content style=\"fixed-case\">D<\/jats:styled-content> inside the ribozyme structure. Neomycin\u00a0<jats:styled-content style=\"fixed-case\">B<\/jats:styled-content>, an aminoglycoside antibiotic, which strongly inhibited the catalytic properties of delta ribozyme, was bound to the pocket formed by the <jats:styled-content style=\"fixed-case\">P<\/jats:styled-content>1 stem, the <jats:styled-content style=\"fixed-case\">P<\/jats:styled-content>1.1 pseudoknot, and the <jats:styled-content style=\"fixed-case\">J<\/jats:styled-content>4\/2 junction. Amikacin showed less effective binding to the ribozyme catalytic core, resulting in weak inhibition. Complexes of these aminoglycosides with <jats:styled-content style=\"fixed-case\">C<\/jats:styled-content>u<jats:sup>2+<\/jats:sup> ions were bound to the same ribozyme regions, but more effectively, showing lower <jats:italic><jats:styled-content style=\"fixed-case\">K<\/jats:styled-content><\/jats:italic><jats:sub>d<\/jats:sub> values. On the other hand, the <jats:styled-content style=\"fixed-case\">C<\/jats:styled-content>u<jats:sup>2+<\/jats:sup> complex of the cyclopeptide antibiotic actinonomycin\u00a0<jats:styled-content style=\"fixed-case\">D<\/jats:styled-content> was preferentially intercalated into the <jats:styled-content style=\"fixed-case\">P<\/jats:styled-content>2 and the <jats:styled-content style=\"fixed-case\">P<\/jats:styled-content>4 double\u2010stranded region, and was three times more potent in ribozyme inhibition than the free antibiotic. In addition, some differences in <jats:styled-content style=\"fixed-case\">SHAPE<\/jats:styled-content> reactivities between the ribozyme forms containing all\u2010<jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content> and deoxycytidine\u2010modified substrates in the <jats:styled-content style=\"fixed-case\">J<\/jats:styled-content>4\/2 region were detected, pointing to different ribozyme conformations before and after the cleavage event.<\/jats:p>","DOI":"10.1111\/febs.12257","type":"journal-article","created":{"date-parts":[[2013,3,25]],"date-time":"2013-03-25T16:21:11Z","timestamp":1364228471000},"page":"2652-2664","update-policy":"http:\/\/dx.doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Mapping the interactions of selected antibiotics and their <scp>C<\/scp>u<sup>2+<\/sup> complexes with the antigenomic delta 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