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Publication Abstract from PubMed

The increase in multi-drug-resistant bacteria is limiting the effectiveness of currently approved antibiotics, leading to a renewed interest in antibiotics with distinct chemical scaffolds. We have solved the structures of the Thermus thermophilus 70S ribosome with A-, P-, and E-site tRNAs bound and in complex with either the aminocyclitol-containing antibiotic hygromycin A (HygA) or the nucleoside antibiotic A201A. Both antibiotics bind at the peptidyl transferase center and sterically occlude the CCA-end of the A-tRNA from entering the A site of the peptidyl transferase center. Single-molecule Forster resonance energy transfer (smFRET) experiments reveal that HygA and A201A specifically interfere with full accommodation of the A-tRNA, leading to the presence of tRNA accommodation intermediates and thereby inhibiting peptide bond formation. Thus, our results provide not only insight into the mechanism of action of HygA and A201A, but also into the fundamental process of tRNA accommodation during protein synthesis.

Distinct tRNA Accommodation Intermediates Observed on the Ribosome with the Antibiotics Hygromycin A and A201A.,Polikanov YS, Starosta AL, Juette MF, Altman RB, Terry DS, Lu W, Burnett BJ, Dinos G, Reynolds KA, Blanchard SC, Steitz TA, Wilson DN Mol Cell. 2015 Jun 4;58(5):832-44. doi: 10.1016/j.molcel.2015.04.014. Epub 2015, May 28. PMID:26028538^[1]

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