Mechanism of Action

The molecular details by which AGs cause miscoding were recently elucidated (61). Nucleotides A1492 and A1493, along with G517, play pivotal roles in discriminating between cognate codon/anticodon interactions and non-cognate interactions. When the correct tRNA occupies the A-site, the tRNA and mRNA nucleotides involved in the codon/anticodon interaction form a regular helix conformation, and consequently normal minor goove geometry. In the correct presentation a helical minor groove stabilizes the "looped-out" conformation of A1492, A1493, and G517, the conformation which serves as a signal for peptide bond formation to occur. Incorrect tRNAs do not elicit the same response and eventually diffuse away from the A-site with out the formation of a new peptide bond. However, when either a 4,5 or 4,6 AG binds to 16S rRNA, it displaces A1492 and A1493 into the "looped-out" conformation. Therefore, peptide bond formation will occur regardless of whether or not the correct tRNA occupies the A-site.

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