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

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

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.

Mandava, Chandra Sekhar,1978-Uppsala universitet,Molekylärbiologi(Swepub:uu)chsma839 (författare)
Ehrenberg, MånsUppsala universitet,Molekylärbiologi(Swepub:uu)mansehre (författare)
Sanyal, SuparnaUppsala universitet,Molekylärbiologi(Swepub:uu)sucsa102 (författare)
Uppsala universitetInstitutionen för cell- och molekylärbiologi (creator_code:org_t)

Av författaren/redakt...: Holm, Mikael, 19 ...; Mandava, Chandra ...; Ehrenberg, Måns; Sanyal, Suparna

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