agmatidine and lysidine

Bacteria and archaea have 2-lysylcytidine (L or lysidine) and 2-agmatinylcytidine (agm(2)C or agmatidine), respectively, at the first (wobble) position of the anticodon of the AUA codon-specific tRNA(Ile). These lysine- or agmatine-conjugated cytidine derivatives are crucial for the precise decoding of the genetic code. L is synthesized by tRNA(Ile)-lysidine synthetase (TilS), which uses l-lysine and ATP as substrates. Agm(2)C formation is catalyzed by tRNA(Ile)-agm(2)C synthetase (TiaS), which uses agmatine and ATP for the reaction. Despite the fact that TilS and TiaS synthesize structurally similar cytidine derivatives, these enzymes belong to non-related protein families. Therefore, these enzymes modify the wobble cytidine by distinct catalytic mechanisms, in which TilS activates the C2 carbon of the wobble cytidine by adenylation, while TiaS activates it by phosphorylation. In contrast, TilS and TiaS share similar tRNA recognition mechanisms, in which the enzymes recognize the tRNA acceptor stem to discriminate tRNA(Ile) and tRNA(Met).

Topics: Archaea; Bacteria; Codon; Cytidine; Lysine; Pyrimidine Nucleosides; RNA, Transfer

Deciphering AUA codons is a difficult task for organisms, because AUA and AUG specify isoleucine (Ile) and methionine (Met), separately. Each of the other purine-ending sense co-don sets (NNR) specifies a single amino acid in the universal genetic code. In bacteria and archaea, the cytidine derivatives, 2-lysylcytidine (L or lysidine) and 2-agmatinylcytidine (agm(2)C or agmatidine), respectively, are found at the first letter of the anticodon of tRNA(Ile) responsible for AUA codons. These modifications prevent base pairing with G of the third letter of AUG codon, and enable tRNA(Ile) to decipher AUA codon specifically. In addition, these modifications confer a charging ability of tRNA(Ile) with Ile. Despite their similar chemical structures, L and agm(2)C are synthesized by distinctive mechanisms and catalyzed by different classes of enzymes, implying that the analogous decoding systems for AUA codons were established by convergent evolution after the phylogenic split between bacteria and archaea-eukaryotes lineages following divergence from the last universal common ancestor (LUCA).

Topics: Anticodon; Archaea; Bacteria; Biological Evolution; Codon; Cytidine; Genetic Code; Isoleucine; Lysine; Methionine; Models, Molecular; Phylogeny; Protein Biosynthesis; Pyrimidine Nucleosides; Ribosomes; RNA, Transfer

An efficient route for the synthesis of 2,4-diaminopyrimidine ribosides from cytidine is described consisting of six steps with overall yields >50% and only one chromatographic step. The key amine addition step utilizes LiCl and 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) to ensure clean conversion to a single tautomeric product. This route has been used to prepare the modified tRNA nucleosides lysidine and agmatidine in quantities suitable for structural characterization.

Topics: Cytidine; Lysine; Molecular Structure; Pyrimidine Nucleosides; Pyrimidines; RNA