The Mechanism of Error Induction by the Antibiotic Viomycin Provides Insight into the Fidelity Mechanism of Translation

Overview

Journal Elife

Specialty Biology

Date 2019 Jun 8

PMID 31172942

Citations 8

Authors

Mikael Holm

Chandra Sekhar Mandava

Mans Ehrenberg

Suparna Sanyal

Affiliations

Soon will be listed here.

Abstract

Applying pre-steady state kinetics to an based reconstituted translation system, we have studied how the antibiotic viomycin affects the accuracy of genetic code reading. We find that viomycin binds to translating ribosomes associated with a ternary complex (TC) consisting of elongation factor Tu (EF-Tu), aminoacyl tRNA and GTP, and locks the otherwise dynamically flipping monitoring bases A1492 and A1493 into their active conformation. This effectively prevents dissociation of near- and non-cognate TCs from the ribosome, thereby enhancing errors in initial selection. Moreover, viomycin shuts down proofreading-based error correction. Our results imply a mechanism in which the accuracy of initial selection is achieved by larger backward rate constants toward TC dissociation rather than by a smaller rate constant for GTP hydrolysis for near- and non-cognate TCs. Additionally, our results demonstrate that translocation inhibition, rather than error induction, is the major cause of cell growth inhibition by viomycin.

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