7s1g

wild-type Escherichia coli stalled ribosome with antibiotic linezolidwild-type Escherichia coli stalled ribosome with antibiotic linezolid

Structural highlights

7s1g is a 10 chain structure with sequence from Escherichia coli. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	Electron Microscopy, Resolution 2.48Å
Ligands:	, , , , , , , , , , , , , , , ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

RL23_ECOLI One of the early assembly proteins, it binds 23S rRNA; is essential for growth. One of the proteins that surround the polypeptide exit tunnel on the outside of the subunit. Acts as the docking site for trigger factor (PubMed:12226666) for Ffh binding to the ribosome (SRP54, PubMed:12756233 and PubMed:12702815) and to nascent polypeptide chains (PubMed:12756233).[HAMAP-Rule:MF_01369]

Publication Abstract from PubMed

The antibiotic linezolid, the first clinically approved member of the oxazolidinone class, inhibits translation of bacterial ribosomes by binding to the peptidyl transferase center. Recent work has demonstrated that linezolid does not inhibit peptide bond formation at all sequences but rather acts in a context-specific manner, namely when alanine occupies the penultimate position of the nascent chain. However, the molecular basis for context-specificity has not been elucidated. Here we show that the second-generation oxazolidinone radezolid also induces stalling with a penultimate alanine, and we determine high-resolution cryo-EM structures of linezolid- and radezolid-stalled ribosome complexes to explain their mechanism of action. These structures reveal that the alanine side chain fits within a small hydrophobic crevice created by oxazolidinone, resulting in improved ribosome binding. Modification of the ribosome by the antibiotic resistance enzyme Cfr disrupts stalling due to repositioning of the modified nucleotide. Together, our findings provide molecular understanding for the context-specificity of oxazolidinones.

Structural basis for context-specific inhibition of translation by oxazolidinone antibiotics.,Tsai K, Stojkovic V, Lee DJ, Young ID, Szal T, Klepacki D, Vazquez-Laslop N, Mankin AS, Fraser JS, Fujimori DG Nat Struct Mol Biol. 2022 Feb;29(2):162-171. doi: 10.1038/s41594-022-00723-9. , Epub 2022 Feb 14. PMID:35165456^[1]

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

References

↑ Tsai K, Stojković V, Lee DJ, Young ID, Szal T, Klepacki D, Vázquez-Laslop N, Mankin AS, Fraser JS, Fujimori DG. Structural basis for context-specific inhibition of translation by oxazolidinone antibiotics. Nat Struct Mol Biol. 2022 Feb;29(2):162-171. PMID:35165456 doi:10.1038/s41594-022-00723-9

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OCA

[1] Tsai K, Stojković V, Lee DJ, Young ID, Szal T, Klepacki D, Vázquez-Laslop N, Mankin AS, Fraser JS, Fujimori DG. Structural basis for context-specific inhibition of translation by oxazolidinone antibiotics. Nat Struct Mol Biol. 2022 Feb;29(2):162-171. PMID:35165456 doi:10.1038/s41594-022-00723-9

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