Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0162871 (abdominal aortic aneurysm)
 8,664 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The redundant genetic codons NNU and NNC (where N is A, T, G, or C) specify the same amino acid and are decoded by their cognate tRNAs, which contain either a guanosine or a modified base in the wobble position of the anticodons. Since tRNAs with an adenosine in the wobble position of the anticodon, which are complementary to the NNU codons, are not found naturally, we have generated a tRNA(Phe) with AAA anticodon and examined how an adenosine in the wobble position would affect its biological function in Escherichia coli. We found that the tRNA(Phe) with GAA anticodon (wild-type) repressed the expression of the pheA gene via tRNA(Phe)-mediated attenuation of transcription, whereas the tRNA(Phe) with AAA anticodon did not influence the expression of the pheA gene. Furthermore, elevated levels of tRNA(Phe)(AAA) did not support the growth of an E. coli strain carrying a temperature-sensitive mutation in the pheS gene at 42 degrees C. Since the presence of a multicopy plasmid carrying the gene that encodes tRNA(Phe)(GAA), a substrate for phenylalanyl tRNA synthetase, enables the E. coli strain carrying the pheS(Ts) mutation to grow at 42 degrees C, the above observation suggests that unlike tRNA(Phe)(GAA), tRNA(Phe)(AAA) is not a good substrate for phenylalanyl-tRNA synthetase. Therefore, we postulate that the presence of adenosine at the wobble position of anticodons was specifically eliminated and the tRNAs with guanosine or a modified base in the wobble position were selected to decode both NNU and NNC codons in E. coli.
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PMID:The tRNA species for redundant genetic codons NNU and NNC. A thought on the absence of phenylalanine tRNA with AAA anticodon in Escherichia coli. 137 Aug 14

A mutant yeast phenylalanine transfer RNA (ytRNAPheAAA) containing a modified (AAA) anticodon was generated to explore the feasibility of breaking the degeneracy of the genetic code in Escherichia coli. By using an E. coli strain co-transformed with ytRNAPheAAA and a mutant yeast phenylalanyl-tRNA synthetase, we demonstrate efficient replacement of phenylalanine (Phe) by L-3-(2-naphthyl)alanine (Nal) at UUU, but not at UUC codons.
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PMID:Breaking the degeneracy of the genetic code. 1281 80

Multiple-site-specific incorporation of a noncanonical amino acid into a recombinant protein would be a very useful technique to generate multiple chemical handles for bioconjugation and multivalent binding sites for the enhanced interaction. Previously combination of a mutant yeast phenylalanyl-tRNA synthetase variant and the yeast phenylalanyl-tRNA containing the AAA anticodon was used to incorporate a noncanonical amino acid into multiple UUU phenylalanine (Phe) codons in a site-specific manner. However, due to the less selective codon recognition of the AAA anticodon, there was significant misincorporation of a noncanonical amino acid into unwanted UUC Phe codons. To enhance codon selectivity, we explored degenerate leucine (Leu) codons instead of Phe degenerate codons. Combined use of the mutant yeast phenylalanyl-tRNA containing the CAA anticodon and the yPheRS_naph variant allowed incorporation of a phenylalanine analog, 2-naphthylalanine, into murine dihydrofolate reductase in response to multiple UUG Leu codons, but not to other Leu codon sites. Despite the moderate UUG codon occupancy by 2-naphthylalaine, these results successfully demonstrated that the concept of forced ambiguity of the genetic code can be achieved for the Leu codons, available for multiple-site-specific incorporation.
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PMID:Forced Ambiguity of the Leucine Codons for Multiple-Site-Specific Incorporation of a Noncanonical Amino Acid. 2702 6