Disease relevance of CARS

• To gain insights into the differences between the bacterial and eukaryotic forms, we previously studied the E. coli cysteinyl-tRNA synthetase [1].
• Selenocysteine was identified as the reduction product by reaction with Gaitonde's reagent, comparison of absorption spectra, paper chromatograhy, utilization by cysteinyl-tRNA synthetase fro Paracoccus denitrificans and Vigna radiata, changes in solubility after DTT treatment, and comparison of infrared spectra [2].

High impact information on CARS

• An experimental system is provided by the recently discovered O-phosphoseryl-tRNA synthetase (SepRS), which acylates tRNA(Cys) with phosphoserine (Sep), and the well known cysteinyl-tRNA synthetase, which charges the same tRNA with cysteine [3].
• We determined the identity elements of Methanocaldococcus jannaschii tRNA(Cys) in the aminoacylation reaction for the two Methanococcus maripaludis synthetases SepRS (forming Sep-tRNA(Cys)) and cysteinyl-tRNA synthetase (forming Cys-tRNA(Cys)) [3].
• Phylogenetic analysis showed the putative class II CysRSs to be a monophyletic group and homology modeling revealed a constellation of active site residues similar to that in the known class I CysRS [4].
• However, the mechanism of Cys-tRNACys formation in three methanogenic archaea ( Methanocaldococcus jannaschii, Methanothermobacter thermautotrophicus and Methanopyrus kandleri) is still unknown, since no recognizable gene for a canonical cysteinyl-tRNA synthetase could be identified in the genome sequences of these organisms [5].
• Rapid amplification of cDNA ends (5'RACE) identified cysteinyl-tRNA synthetase (CARS) gene fused to ALK, which predicts an in-frame chimeric protein with the preserved functional catalytic domain of ALK at the C terminus [6].

Biological context of CARS

• Nucleotide and deduced amino acid sequence of human cysteinyl-tRNA synthetase [7].
• The predicted protein sequence of 638 amino acids has substantial sequence similarity to the E. coli cysteinyl-tRNA synthetase in the nucleotide-binding fold region that constitutes the potential active site [7].
• An elongation factor-associating domain is inserted into human cysteinyl-tRNA synthetase by alternative splicing [8].
• We have determined the nucleotide sequence of a cDNA coding human cysteinyl-tRNA synthetase [7].
• The amino acid sequence of human cytoplasmic cysteinyl-tRNA synthetase (CRS) was examined by analyzing sequences of genomic and expressed sequence tag fragments [8].

Anatomical context of CARS

• Similar alterations to the transit peptides of histidyl- or cysteinyl-tRNA synthetase, which are dual-targeted to chloroplasts and mitochondria, had no effect on their ability to target green fluorescent protein in vivo [9].

Associations of CARS with chemical compounds

• Cysteinyl-tRNA synthetase catalyzes the addition of cysteine to its cognate tRNA [1].
• Using sequence-profile analysis, multiple alignment and secondary-structure prediction, we have identified the unique archaeal 'cysteinyl-tRNA synthetase' as a homolog of extracellular polygalactosaminidases, and the 'dihydropteroate synthase' as a member of the beta-lactamase-like superfamily of metal-dependent hydrolases [10].

Other interactions of CARS

• The most unusual cases involved the identification of an archaeal cysteinyl-tRNA synthetase, a dihydropteroate synthase and a thymidylate synthase, for which experimental verifications of apparently erroneous computational predictions were reported [10].

Analytical, diagnostic and therapeutic context of CARS

• For one CysRS and one AsnRS, sequence alignments and prediction programs suggested the presence of an N-terminal organellar targeting peptide [11].

References