On the mechanism of translation error induction by aminoglycoside antibiotics
(English)Manuscript (preprint) (Other academic)
We used a cell-free system with pure Escherichia coli components to study how the aminoglycosides disrupt initial codon selection of aminoacyl-tRNAs in ternary complex with elongation factor Tu and GTP by messenger RNA-programmed ribosomes. We take the advantage of the universal rate-accuracy trade-off for all enzymatic selections to determine how the efficiency of initial codon readings decreased linearly toward zero as the accuracy of discrimination against near cognate and wobble codon readings increased toward the maximal asymptote, the effective d value. It turns out two ribosome bound states of ternary complex. First, one codon non-selective step, Mg2+ ions shift the equilibrium from free to ribosome bound ternary complex meaning that the equilibrium between the two ribosome bound complexes is unaltered. Second, codon selective step, aminoglycosides shift the equilibrium from codon non-selective to codon selective complex meaning that the equilibrium between the free and the codon non-selective state is unchanged.
protein synthesis, genetic code, misreading, kinitics, aminoglycosides, decoding
Biochemistry and Molecular Biology
IdentifiersURN: urn:nbn:se:uu:diva-265304OAI: oai:DiVA.org:uu-265304DiVA: diva2:865097