Possible conformations of 5-aminomethyluridine derivatives recognizing a G at the third position of the codon

Specificity of the codon-anticodon interaction is often modulated by post-transcriptional modification at the first position of the anticodon (position 34) of the tRNA molecules. The modification of U(34) into 5-aminomethyluridine derivatives facilitates the pairing of the base with a G at the third position of the codon (position III). It was proposed that this wobble pairing is dependent on the deprotonation of the uridine derivative [Takai and Yokoyama, Nucleic Acids Res., 31, 6383-6391 (2003)]. This seemed to explain many results from biochemical and genetic experiments. On the other hand, however, the geometry of the base pair between 5-methylaminomethyluridine and G(III) in a crystal of the ribosomal 30S subunit was quite different from the predicted one [Murphy IV et al., Nat. Struct. Mol. Biol., 11, 1186-1191 (2004)]. It is obvious that the deprotonation, if any, should be inefficient at the pH at which the crystal was made. Therefore, the crystal structure does not exclude the possibility that the pairs are primarily dependent on the deprotonation of the modified uridines at the physiological pH.