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Browsing by Subject "23S ribosomal RNA"

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    NMR characterisation of the antibiotic resistance-mediating 32mer RNA from the 23S ribosomal RNA
    2025-02-26
    Muhs, Christina 
    Lena Kemper
    Wacker, Anna
    Schwalbe, Harald Jochen 
    Richter, Christian 
    Francesca Lavore
    Markus Weingarth
    The increasing prevalence of antibiotic resistance represents a significant public health concern, underscoring the urgent need for the development of novel therapeutic strategies. Macrolides, the second most widely used class of antibiotics, are inhibited by Erm-proteins through the methylation of adenosine 2058 of the 23S ribosomal RNA (rRNA) (~2900 nucleotides). This methylation is the molecular basis for preventing macrolides from binding and bacteria (Staphylococcus, Streptococcus and Enterococcus) developing resistance. While Erm-proteins have received considerable attention, the role of the ribosomal RNA in acquiring antibiotic resistance is frequently undervalued, even though the ribosomal RNA is the chemical target for methylation. Here, we present the comprehensive resonance assignment for 1H, 13C and 15N for the part of the 23S RNA that serves as the Erm substrate in antimicrobial resistance by solution NMR spectroscopy. Furthermore, we compare the chemical shift signature of the methylated and dimethylated RNA construct and show that changes in the RNA upon methylation are locally restricted. The chemical shift assignments provide a starting point for investigating and targeting the molecular mechanism of the resistance-conferring Erm proteins.
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