Anticodon-codon interactions

It has been known for some time that tetracyclines are accumulated by bacteria and prevent bacterial protein synthesis (Fig. 4). Furthermore, inhibition of protein synthesis is responsible for the bacteriostatic effect (85). Inhibition of protein synthesis results primarily from dismption of codon-anticodon interaction between tRNA and mRNA so that binding of aminoacyl-tRNA to the ribosomal acceptor (A) site is prevented (85). The precise mechanism is not understood. However, inhibition is likely to result from interaction of the tetracyclines with the 30S ribosomal subunit because these antibiotics are known to bind strongly to a single site on the 30S subunit (85). 

What is the importance of this enzyme family for the biogenesis problem These enzymes form the link between the protein world and the nucleic acid world . They catalyse the reaction between amino acids and transfer RNA molecules, which includes an activation step involving ATR The formation of the peptide bond, i.e., the actual polycondensation reaction, takes place at the ribosome and involves mRNA participation and process control via codon-anticodon interaction. 

Figure 3 Cognate and near-cognate codon-anticodon interactions. The anticodon ioop of tRNA is shown as an example interacting with various codons on the mRNA. In correct, cognate codon-anticodon pairings, two Watson-Crick base pairs can be formed in the first two positions while the third position contains either a Watson-Crick or a wobble base pair.

Another pairing that occurs in tRNAs allows guanine to pair with uracil, e.g., G4 with U69. This was originally proposed to account for codon-anticodon interactions betweentRNA molecules and messenger RNA (Chapter 29). It is commonly called wobble pairing because the uracil must wobble away from its orientation in the normal Watson-Crick pair.27 37... 

Not all aminoacyl-tRNA synthetases have editing sites. The cysteinyl- and tyrosyl-tRNA synthetases bind the correct substrates so much more tightly than their competitors that they do not need to edit.13,14 Similarly, since the accuracy of transcription of DNA by RNA polymerase is better than the overall observed error rate in protein synthesis at about 1 part in 104, RNA polymerases do not need to edit.15 The same should be true for codon-anticodon interactions on the ribosome. However, it is possible that accuracy has been sacrificed to achieve higher rates in this case, which is analogous to a change from Michaelis-Menten to Briggs-Haldane kinetics, and so an editing step is required.16... 

The start of protein synthesis is signalled by specific codon-anticodon interactions. Termination is also signalled by a codon in the mRNA, although the stop signal is not recognized by tRNA, but by proteins that then trigger the hydrolysis of the completed polypeptide chain from the tRNA. Just how the secondary and tertiary structures of the proteins are achieved is not yet clear, but certainly the mechanism of protein synthesis, which we have outlined here, requires little modification to account for preferential formation of particular conformations. 

The Code Was Deciphered with the Help of Synthetic Messengers The Code Is Highly Degenerate Wobble Introduces Ambiguity into Codon-Anticodon Interactions... 

Wobble Introduces Ambiguity into Codon-Anticodon Interactions... 

The 3 terminal redundancy of the genetic code and its mechanistic basis were first appreciated by Francis Crick in 1966. He proposed that codons and anticodons interact in an antiparallel manner on the ribosome in such a way as to require strict Watson-Crick pairing (that is, A-U and G-C) in the first two positions of the codon but to allow other pairings in its 3 terminal position. Nonstandard base pairing between the 3 terminal position of the codon and the 5 terminal position of the anticodon alters the geometry between the paired bases Crick s proposal, labeled the wobble hypothesis, is now viewed as correctly describing the codon-anticodon interactions that underlie the translation of the genetic code. 

The codon-anticodon interaction is limited to Watson-Crick pairing for the first two bases in the codon but is considerably more flexible in the third position. 

Fidelity in Codon-Anticodon Interaction. Nature. 1976, 263, 289-293. Opposing view Orozco, M., Hernandez, B., Luque, F. J. Tautomerization of 1-Methyl Derivatives of Uracil, Thymine, and 5-Bromouracil. Is Tautomerization the Basis for the Mutagenicity of 5-Bromouridine J. Phys. Chem. B. 1998,102, 5228-5233.)... 

Y3. Yasukawa, T., Suzuki, T., Ishii, N., Ohta, S., and Watanabe, K., Wobble modification defect in tRNA disturbs codon-anticodon interaction in a mitochondrial disease. EMBO J. 20,4794-4802 (2001). 

Fig. 16.14. The wobble G-U base pair GU22 formed by guanine and uracil is of importance in the codon-anticodon interaction between messenger RNA and transfer RNA...

Ibpal MD, Fresco JR (1976) Base-pairing and fidelity in codon-anticodon interaction. Nature (Lond) 263 289- 293... 

Only the Codon-Anticodon Interactions Determine the Amino Acid That Is Incorporated... 

Two generalizations concerning the codon-anticodon interaction can be made. 

Once an amino add is attached to a tRNA, insertion of the amino add into a growing polypeptide chain depends only on the codon-anticodon interaction (Figure 3-24). 

Chlortetracyclin inhibits protein synthesis by binding to the 30S subunit of ribosomes and prevents the aminoacyl-tRNA binding to the A site on the ribosome. This prevents the codon-anticodon interaction from taking place. Protein release is also inhibited. 

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