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7lh5

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

Structural highlights

7lh5 is a 20 chain structure with sequence from Thermus thermophilus HB8. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 3.27Å
Ligands:	, ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

RL31_THET8 Binds the 23S rRNA (By similarity).[HAMAP-Rule:MF_00501]

Publication Abstract from PubMed

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.

Structural basis for plazomicin antibiotic action and resistance.,Golkar T, Bassenden AV, Maiti K, Arya DP, Schmeing TM, Berghuis AM Commun Biol. 2021 Jun 11;4(1):729. doi: 10.1038/s42003-021-02261-4. PMID:34117352^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Golkar T, Bassenden AV, Maiti K, Arya DP, Schmeing TM, Berghuis AM. Structural basis for plazomicin antibiotic action and resistance. Commun Biol. 2021 Jun 11;4(1):729. doi: 10.1038/s42003-021-02261-4. PMID:34117352 doi:http://dx.doi.org/10.1038/s42003-021-02261-4