The oxazolidinone antibiotics perturb the ribosomal peptidyl-transferase center and effect tRNA positioning.

Abstract:

:The oxazolidinones represent the first new class of antibiotics to enter into clinical usage within the past 30 years, but their binding site and mechanism of action has not been fully characterized. We have determined the crystal structure of the oxazolidinone linezolid bound to the Deinococcus radiodurans 50S ribosomal subunit. Linezolid binds in the A site pocket at the peptidyltransferase center of the ribosome overlapping the aminoacyl moiety of an A-site bound tRNA as well as many clinically important antibiotics. Binding of linezolid stabilizes a distinct conformation of the universally conserved 23S rRNA nucleotide U2585 that would be nonproductive for peptide bond formation. In conjunction with available biochemical data, we present a model whereby oxazolidinones impart their inhibitory effect by perturbing the correct positioning of tRNAs on the ribosome.

authors

Wilson DN,Schluenzen F,Harms JM,Starosta AL,Connell SR,Fucini P

doi

10.1073/pnas.0804276105

subject

Has Abstract

pub_date

2008-09-09 00:00:00

pages

13339-44

issue

36

eissn

0027-8424

issn

1091-6490

pii

0804276105

journal_volume

105

pub_type

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