Orthoformimycin inhibits translation elongation by displacing the A-site tRNA and preventing peptide bond formation

Schedlbauer, A.; Kaminishi, T.; Fabbretti, A.; Milon, P.; Han, X.; Ochoa-Lizarralde, B.; Capuni, R.; Gualerzi, C. O.; Connell, S. R.; Fucini, P.

doi:10.1101/2021.11.29.470217

bioRxiv · 10.1101/2021.11.29.470217

Orthoformimycin inhibits translation elongation by displacing the A-site tRNA and preventing peptide bond formation

Schedlbauer, A.·Kaminishi, T.·Fabbretti, A.·Milon, P.·Han, X.·Ochoa-Lizarralde, B.·Capuni, R.·Gualerzi, C. O.·Connell, S. R.·Fucini, P.

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Abstract

The ribosome is a major target for antibiotics owing to its essential cellular role in protein synthesis. Structural analysis of ribosome-antibiotic complexes provides insight into the molecular basis for their inhibitory action and highlights possible avenues to improve their potential or overcome existing resistance mechanisms. Here we use X-ray crystallography and pre-steady state kinetics to detail the inhibitory mechanism of the antimicrobial on the large ribosomal subunit.

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Schedlbauer, A., Kaminishi, T., Fabbretti, A., Milon, P., Han, X., Ochoa-Lizarralde, B., Capuni, R., Gualerzi, C. O., Connell, S. R., Fucini, P.. 2021-11-29. Orthoformimycin inhibits translation elongation by displacing the A-site tRNA and preventing peptide bond formation. https://doi.org/10.1101/2021.11.29.470217

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