Structural basis for potent inhibitory activity of the antibiotic tigecycline during protein synthesis
Abstract
Here we present an X-ray crystallography structure of the clinically relevant tigecycline antibiotic bound to the 70S ribosome. Our structural and biochemical analysis indicate that the enhanced potency of tigecycline results from a stacking interaction with nucleobase C1054 within the decoding site of the ribosome. Single-molecule fluorescence resonance energy transfer studies reveal that, during decoding, tigecycline inhibits the initial codon recognition step of tRNA accommodation and prevents rescue by the tetracycline-resistance protein TetM.
- Publication:
-
Proceedings of the National Academy of Science
- Pub Date:
- March 2013
- DOI:
- 10.1073/pnas.1216691110
- Bibcode:
- 2013PNAS..110.3812J