Structural basis for aminoglycoside inhibition of bacterial ribosome recycling.

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Borovinskaya MA, Pai RD, Zhang W, Schuwirth BS, Holton JM, Hirokawa G, Kaji H, Kaji A, Cate JH

Structural basis for aminoglycoside inhibition of bacterial ribosome recycling.

Nat Struct Mol Biol. 2007 Aug;14(8):727-32. doi: 10.1038/nsmb1271. Epub 2007 Jul 29.

PubMed ID

17660832 [View in PubMed

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Abstract

Aminoglycosides are widely used antibiotics that cause messenger RNA decoding errors, block mRNA and transfer RNA translocation, and inhibit ribosome recycling. Ribosome recycling follows the termination of protein synthesis and is aided by ribosome recycling factor (RRF) in bacteria. The molecular mechanism by which aminoglycosides inhibit ribosome recycling is unknown. Here we show in X-ray crystal structures of the Escherichia coli 70S ribosome that RRF binding causes RNA helix H69 of the large ribosomal subunit, which is crucial for subunit association, to swing away from the subunit interface. Aminoglycosides bind to H69 and completely restore the contacts between ribosomal subunits that are disrupted by RRF. These results provide a structural explanation for aminoglycoside inhibition of ribosome recycling.

DrugBank Data that Cites this Article

Drugs

Tobramycin

通用电气ntamicin

Streptomycin

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
通用电气ntamicin	23S ribosomal RNA	Nucleotide	Enteric bacteria and other eubacteria	Yes	Inhibitor	Details
Streptomycin	23S ribosomal RNA	Nucleotide	Enteric bacteria and other eubacteria	Yes	Inhibitor	Details
Tobramycin	23S ribosomal RNA	Nucleotide	Enteric bacteria and other eubacteria	Yes	Inhibitor	Details