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Macrolide antibiotics allosterically predispose the ribosome for translation arrest.


ABSTRACT: Translation arrest directed by nascent peptides and small cofactors controls expression of important bacterial and eukaryotic genes, including antibiotic resistance genes, activated by binding of macrolide drugs to the ribosome. Previous studies suggested that specific interactions between the nascent peptide and the antibiotic in the ribosomal exit tunnel play a central role in triggering ribosome stalling. However, here we show that macrolides arrest translation of the truncated ErmDL regulatory peptide when the nascent chain is only three amino acids and therefore is too short to be juxtaposed with the antibiotic. Biochemical probing and molecular dynamics simulations of erythromycin-bound ribosomes showed that the antibiotic in the tunnel allosterically alters the properties of the cat

SUBMITTER: Sothiselvam S 

PROVIDER: S-EPMC4103360 | biostudies-literature | 2014 Jul

REPOSITORIES: biostudies-literature