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An initial screen of 17 RNA\u2010binding antibiotics showed that a number of aminoglycosides inhibit the ribozyme, while a subset of aminoglycosides enhances twister cleavage. Initial kinetic analysis of the twister ribozyme showed a sevenfold inhibition of ribozyme cleavage by paromomycin and a fivefold enhancement of cleavage by sisomicin. Direct binding between the twister ribozyme RNA and paromomycin or sisomicin was measured by microscale thermophoresis. Selective 2\u2032\u2010hydroxyl acylation analysed by primer extension shows that both paromomycin and sisomicin induce distinctive tertiary structure changes to the twister ribozyme. Published crystal structures and mechanistic analysis of the twister ribozyme have deduced a nucleobase\u2010mediated general acid\u2013base catalytic mechanism, in which a conserved guanine plays a key role. Here, we show that paromomycin binding induces a structural transition to the twister ribozyme such that a highly conserved guanine in the active site becomes displaced, leading to inhibition of cleavage. In contrast, sisomicin binding appears to change interactions between P3 and L2, inducing allosteric changes to the active site that enhance twister RNA cleavage. Therefore, we show that small\u2010molecule binding can modulate twister ribozyme activity. These results suggest that aminoglycosides may be used as molecular tools to study this widely distributed ribozyme.<\/jats:p>","DOI":"10.1111\/febs.15517","type":"journal-article","created":{"date-parts":[[2020,8,13]],"date-time":"2020-08-13T14:09:22Z","timestamp":1597327762000},"page":"1586-1598","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Aminoglycoside antibiotics can inhibit or activate twister ribozyme cleavage"],"prefix":"10.1111","volume":"288","author":[{"given":"Jun","family":"Zhang","sequence":"first","affiliation":[{"name":"Fudan University Pudong Medical Center, and Institutes of Biomedical Sciences Shanghai Medical College, Fudan University Shanghai China"},{"name":"Key Laboratory of Metabolism and Molecular Medicine Ministry of Education School of Basic Medical Sciences Fudan University Shanghai 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