7LH5

Crystal structure of the Thermus thermophilus 70S ribosome in complex with plazomicin, mRNA and tRNAs

This is a non-PDB format compatible entry.

Summary for 7LH5

• Entry DOI: 10.2210/pdb7lh5/pdb
• Descriptor: 16S ribosomal RNA, 30S ribosomal protein S10, 30S ribosomal protein S11, ... (62 entities in total)
• Functional Keywords: 70s ribosome, plazomicin, antibiotic resistance, aminoglycoside, ribosome
• Biological source: Escherichia coli; More
• Total number of polymer chains: 118
• Total formula weight: 4589368.96

Authors

Golkar, T.,Berghuis, A.M.,Schmeing, T.M. (deposition date: 2021-01-21, release date: 2021-06-02, Last modification date: 2024-10-30)

Primary citation

Golkar, T.,Bassenden, A.V.,Maiti, K.,Arya, D.P.,Schmeing, T.M.,Berghuis, A.M.
Structural basis for plazomicin antibiotic action and resistance.
Commun Biol, 4:729-729, 2021

PubMed Abstract: The approval of plazomicin broadened the clinical library of aminoglycosides available for use against emerging bacterial pathogens. Contrarily to other aminoglycosides, resistance to plazomicin is limited; still, instances of resistance have been reported in clinical settings. Here, we present structural insights into the mechanism of plazomicin action and the mechanisms of clinical resistance. The structural data reveal that plazomicin exclusively binds to the 16S ribosomal A site, where it likely interferes with the fidelity of mRNA translation. The unique extensions to the core aminoglycoside scaffold incorporated into the structure of plazomicin do not interfere with ribosome binding, which is analogously seen in the binding of this antibiotic to the AAC(2')-Ia resistance enzyme. The data provides a structural rationale for resistance conferred by drug acetylation and ribosome methylation, i.e., the two mechanisms of resistance observed clinically. Finally, the crystal structures of plazomicin in complex with both its target and the clinically relevant resistance factor provide a roadmap for next-generation drug development that aims to ameliorate the impact of antibiotic resistance.

PubMed: 34117352
DOI: 10.1038/s42003-021-02261-4

Experimental method

X-RAY DIFFRACTION (3.27 Å)