The mechanism of error induction by the antibiotic viomycin provides insight into the fidelity mechanism of translation

Holm, Mikael, 1984- (author): Uppsala universitet,Institutionen för cell- och molekylärbiologi

Mandava, Chandra Sekhar, 1978- (author): Uppsala universitet,Molekylärbiologi

(creator_code:org_t)

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Abstract Subject headings

Applying pre-steady state kinetics to an Escherichia-coli-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.

By the author/editor: Holm, Mikael, 19 ...; Mandava, Chandra ...; Ehrenberg, Måns; Sanyal, Suparna

About the subject

NATURAL SCIENCES: NATURAL SCIENCES; and Biological Scien ...; and Biochemistry and ...

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