Characterization of a novel natural tetracenomycin reveals crucial role of 4-hydroxy group in ribosome bindingстатья
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Дата последнего поиска статьи во внешних источниках: 23 марта 2023 г.
Аннотация:The aromatic polyketides tetracenomycins were recently found to be potent inhibitors of protein synthesis. Their binding site is located in a unique locus within the tunnel of the large ribosomal subunit. Here we report the isolation and structure elucidation of a novel natural tetracenomycin congener – O4–Me-tetracenomycin C (O4–Me-TcmC). This compound is isomeric to tetracenomycin X (TcmX), however, in contrast to TcmX, O4–Me-TcmC exhibited no antimicrobial activity and was unable to inhibit protein synthesis in vitro. Structural alignment of tetracenomycins to the binding locus from cryo-EM TcmX-70S ribosome data revealed the crucial role of the 4-hydroxyl group. These findings are important for further development of semi-synthetic tetracenomycins as potential antibacterials.