Disease relevance of DARS

• Expression of human aspartyl-tRNA synthetase in Escherichia coli. Functional analysis of the N-terminal putative amphiphilic helix [1].
• Here, we report the first characterization of the ND-AspRS from the human pathogen Helicobacter pylori (H. pylori or Hp) [2].
• The nondiscriminating aspartyl-tRNA synthetase from Helicobacter pylori: anticodon-binding domain mutations that impact tRNA specificity and heterologous toxicity [2].
• These include the plant sweetening protein, thaumatin, from Thaumatococcus daniellii; the aspartyl-tRNA synthetase from Thermus thermophilus; and pea lectin from Pisum sativum [3].
• Asparaginyl-tRNA formation in Pseudomonas aeruginosa PAO1 involves a nondiscriminating aspartyl-tRNA synthetase (ND-AspRS) which forms Asp-tRNA(Asp) and Asp-tRNA(Asn), and a tRNA-dependent amidotransferase which transamidates the latter into Asn-tRNA(Asn) [4].

High impact information on DARS

• Mitochondrial aspartyl-tRNA synthetase deficiency causes leukoencephalopathy with brain stem and spinal cord involvement and lactate elevation [5].
• We illustrate both molecular dynamics and Poisson-Boltzmann methods with a detailed study of amino acid recognition by aspartyl-tRNA synthetase, whose specificity is important for maintaining the integrity of the genetic code [6].
• While the overall structure of SmpB appears to be unique, the structure does contain an embedded oligonucleotide binding fold; in this respect SmpB has similarity to several other RNA-binding proteins that are known to be associated with translation, including IF1, ribosomal protein S17 and the N-terminal domain of aspartyl tRNA synthetase [7].
• The active site of yeast aspartyl-tRNA synthetase: structural and functional aspects of the aminoacylation reaction [8].
• We show here that small RNA helices which recapitulate part or all of the acceptor stem of yeast aspartate tRNA are efficiently aminoacylated by cognate class II aspartyl-tRNA synthetase [9].

Biological context of DARS

• The kinetics of the aspartylation of tRNA was consistent with the following reaction pathway, [formula: see text] where E, represents aspartyl-tRNA synthetase [10].
• The full length cDNA encodes an open reading frame of 500 amino acids with 56% identity with yeast aspartyl-tRNA synthetase [11].
• Efficient aminoacylation of resected RNA helices by class II aspartyl-tRNA synthetase dependent on a single nucleotide [9].

Anatomical context of DARS

• Expression of human aspartyl-tRNA synthetase in COS cells [12].

Associations of DARS with chemical compounds

• Full-length human AspRS, but not amino-terminal 32 residue-deleted, fully active AspRS, was found to bind to noncognate tRNA(fMet) in the presence of Mg(2+) [13].
• Thus, in addition to their structural and catalytic roles, the Mg2+ cations contribute to specificity in AspRS through long range electrostatic interactions with the Asp side chain in both the pre- and post-adenylation states [14].
• Molecular dynamics simulations show that bound Mg2+ contributes to amino acid and aminoacyl adenylate binding specificity in aspartyl-tRNA synthetase through long range electrostatic interactions [14].
• Replacing this glycine by an aspartate renders human mt-AspRS more discriminative to G73 [15].
• To obtain insight into the origin of the specificity, the binding to aspartyl-tRNA synthetase (AspRS) of the negatively charged substrate aspartic acid and the neutral analogue asparagine are compared by use of molecular dynamics and free energy simulations [16].

Other interactions of DARS

• The selected peptide appendices ranged from 22 aa of aspartyl-tRNA synthetase to 267 aa of methionyl-tRNA synthetase [17].
• Characterization of a novel N-terminal peptide in human aspartyl-tRNA synthetase. Roles in the transfer of aminoacyl-tRNA from aminoacyl-tRNA synthetase to the elongation factor 1 alpha [18].
• The simulations are analyzed to determine the interactions that Asn is able to make in the binding pocket, and which sequence differences between AspRS and the highly homologous AsnRS are important for modifying the amino acid specificity [16].
• Other class II enzymes, aspartyl-tRNA synthetase and seryl-tRNA synthetase, do not edit any of the amino acids tested [19].
• Tessellator, a cross-platform implementation of the algorithm, is used to analyze the cavities within myoglobin, the protein-RNA docking interface between aspartyl-tRNA synthetase and tRNA(Asp), and the ammonia channel in the hisH-hisF complex of imidazole glycerol phosphate synthase [20].

References