aspartate trna ligase


Summary: An enzyme that activates aspartic acid with its specific transfer RNA. EC

Top Publications

  1. Beaulande M, Tarbouriech N, Hartlein M. Human cytosolic asparaginyl-tRNA synthetase: cDNA sequence, functional expression in Escherichia coli and characterization as human autoantigen. Nucleic Acids Res. 1998;26:521-4 pubmed
    ..The human asparaginyl-tRNA synthetase appears to be like the alanyl- and histidyl-tRNA synthetases another example of a human Class II aminoacyl-tRNA synthetase involved in autoimmune reactions. ..
  2. Tsibulskaya D, Mokina O, Kulikovsky A, Piskunova J, Severinov K, Serebryakova M, et al. The Product of Yersinia pseudotuberculosis mcc Operon Is a Peptide-Cytidine Antibiotic Activated Inside Producing Cells by the TldD/E Protease. J Am Chem Soc. 2017;139:16178-16187 pubmed publisher
    ..coli microcin C. Proteolytic processing inside producing cells is a novel strategy of peptide-nucleotide antibiotics biosynthesis that may help control production levels and avoid toxicity to the producer...
  3. Lorber B, Théobald Dietrich A, Charron C, Sauter C, Ng J, Zhu D, et al. From conventional crystallization to better crystals from space: a review on pilot crystallogenesis studies with aspartyl-tRNA synthetases. Acta Crystallogr D Biol Crystallogr. 2002;58:1674-80 pubmed
    ..Usefulness for structural biology of targeted methods aimed to improve the intrinsic physical quality of protein crystals is highlighted. ..
  4. Ponting C, Mott R, Bork P, Copley R. Novel protein domains and repeats in Drosophila melanogaster: insights into structure, function, and evolution. Genome Res. 2001;11:1996-2008 pubmed
    ..These findings demonstrate how completely sequenced genomes can be exploited to further understand the relationships between molecular structure, function, and evolution. ..
  5. Gatti D, Tzagoloff A. Structure and evolution of a group of related aminoacyl-tRNA synthetases. J Mol Biol. 1991;218:557-68 pubmed
  6. Kron M, Petridis M, Milev Y, Leykam J, Hartlein M. Expression, localization and alternative function of cytoplasmic asparaginyl-tRNA synthetase in Brugia malayi. Mol Biochem Parasitol. 2003;129:33-9 pubmed
    ..These data support the hypothesis that all AARS are not equally expressed in B. malayi and that these enzymes may demonstrate important alternative functions in filaria. ..
  7. Beaulande M, Kron M, Hirakata M, Hartlein M. Human anti-asparaginyl-tRNA synthetase autoantibodies (anti-KS) increase the affinity of the enzyme for its tRNA substrate. FEBS Lett. 2001;494:170-4 pubmed
  8. Shiba K, Motegi H, Yoshida M, Noda T. Human asparaginyl-tRNA synthetase: molecular cloning and the inference of the evolutionary history of Asx-tRNA synthetase family. Nucleic Acids Res. 1998;26:5045-51 pubmed
  9. McClain W, Gabriel K. Construction of an Escherichia coli knockout strain for functional analysis of tRNA(Asp). J Mol Biol. 2001;310:537-42 pubmed
    ..We have developed a system to overcome this deficiency by engineering an E. coli knockout tRNA(Asp) strain, thereby allowing a penetrating analysis of tRNA(Asp) structure and function under conditions that prevail in the cell. ..

More Information


  1. Novikova M, Metlitskaya A, Datsenko K, Kazakov T, Kazakov A, Wanner B, et al. The Escherichia coli Yej transporter is required for the uptake of translation inhibitor microcin C. J Bacteriol. 2007;189:8361-5 pubmed
    ..coli. Other substrates of YejABEF remain to be identified...
  2. Metlitskaya A, Kazakov T, Vondenhoff G, Novikova M, Shashkov A, Zatsepin T, et al. Maturation of the translation inhibitor microcin C. J Bacteriol. 2009;191:2380-7 pubmed publisher
    ..We show that the products of the mccD and mccE genes are required for attachment of a 3-aminopropyl group to the phosphate of McC and that this group increases the potency of inhibition of the McC target, aspartyl-tRNA synthetase. ..
  3. Thompson D, Simonson T. 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. J Biol Chem. 2006;281:23792-803 pubmed
    ..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. ..
  4. Petoukhov M, Svergun D. Joint use of small-angle X-ray and neutron scattering to study biological macromolecules in solution. Eur Biophys J. 2006;35:567-76 pubmed
    ..The efficiency of the methods is demonstrated in model examples, and potential sources of ambiguity are discussed. ..
  5. Charri re F, O Donoghue P, Helgad ttir S, Mar chal Drouard L, Cristodero M, Horn E, et al. Dual targeting of a tRNAAsp requires two different aspartyl-tRNA synthetases in Trypanosoma brucei. J Biol Chem. 2009;284:16210-7 pubmed publisher
    ..Mitochondrial Tb-AspRS2 defines a novel group of eukaryotic AspRSs with an expanded substrate specificity that are restricted to trypanosomatids and therefore may be exploited as a novel drug target...
  6. Guignard L, Ozawa K, Pursglove S, Otting G, Dixon N. NMR analysis of in vitro-synthesized proteins without purification: a high-throughput approach. FEBS Lett. 2002;524:159-62 pubmed
    ..As cell-free protein expression provides high yields of protein per unit mass of labeled amino acid and sample handling is minimal, this strategy presents an exceptionally inexpensive and rapid approach to protein analysis. ..
  7. Escalante C, Yang D. Expression of human aspartyl-tRNA synthetase in Escherichia coli. Functional analysis of the N-terminal putative amphiphilic helix. J Biol Chem. 1993;268:6014-23 pubmed
    ..The structure and function of the N-terminal peptide in aspartyl-tRNA synthetase and in the synthetase complex will be discussed. ..
  8. Conrath U, Beckers G, Langenbach C, Jaskiewicz M. Priming for enhanced defense. Annu Rev Phytopathol. 2015;53:97-119 pubmed publisher
  9. Martin F, Eriani G, Eiler S, Moras D, Dirheimer G, Gangloff J. Overproduction and purification of native and queuine-lacking Escherichia coli tRNA(Asp). Role of the wobble base in tRNA(Asp) acylation. J Mol Biol. 1993;234:965-74 pubmed
    ..coli, where only one contact is thought to occur at position 34. ..
  10. Soutourina J, Plateau P, Blanquet S. Metabolism of D-aminoacyl-tRNAs in Escherichia coli and Saccharomyces cerevisiae cells. J Biol Chem. 2000;275:32535-42 pubmed
    ..This observation suggests that, in yeast, at least two d-amino acids succeed in being transferred onto tRNAs and that, like in E. coli, the resulting two d-aminoacyl-tRNAs are substrates of a same d-aminoacyl-tRNA deacylase. ..
  11. Scheper G, van der Klok T, van Andel R, van Berkel C, Sissler M, Smet J, et al. Mitochondrial aspartyl-tRNA synthetase deficiency causes leukoencephalopathy with brain stem and spinal cord involvement and lactate elevation. Nat Genet. 2007;39:534-9 pubmed
    ..We were surprised to find that activities of mitochondrial complexes from fibroblasts and lymphoblasts derived from affected individuals were normal, as determined by different assays. ..
  12. Mirande M, Waller J. Molecular cloning and primary structure of cDNA encoding the catalytic domain of rat liver aspartyl-tRNA synthetase. J Biol Chem. 1989;264:842-7 pubmed
    ..The primary structure of the DRS1 gene product is discussed in relation to the occurrence of two distinct forms of that enzyme. ..
  13. Kolman C, Snyder M, Soll D. Genomic organization of tRNA and aminoacyl-tRNA synthetase genes for two amino acids in Saccharomyces cerevisiae. Genomics. 1988;3:201-6 pubmed
    ..We have supported and expanded this view by applying the facile method of contour-clamped homogeneous electric field gel electrophoresis to the investigation of these small multigene families. ..
  14. Ryckelynck M, Masquida B, Giege R, Frugier M. An intricate RNA structure with two tRNA-derived motifs directs complex formation between yeast aspartyl-tRNA synthetase and its mRNA. J Mol Biol. 2005;354:614-29 pubmed
    ..In the recognition process, the N-terminal extension of each AspRS subunit plays a crucial role in anchoring the tRNA-like motifs of the mRNA on the synthetase. ..
  15. O Donoghue P, Luthey Schulten Z. Evolutionary profiles derived from the QR factorization of multiple structural alignments gives an economy of information. J Mol Biol. 2005;346:875-94 pubmed
  16. Bour T, Akaddar A, Lorber B, Blais S, Balg C, Candolfi E, et al. Plasmodial aspartyl-tRNA synthetases and peculiarities in Plasmodium falciparum. J Biol Chem. 2009;284:18893-903 pubmed publisher
    ..These data provide a robust background for unraveling the precise functional properties of the parasite AspRS and for developing novel lead compounds against malaria, targeting its idiosyncratic domains...
  17. Tumbula Hansen D, Feng L, Toogood H, Stetter K, S ll D. Evolutionary divergence of the archaeal aspartyl-tRNA synthetases into discriminating and nondiscriminating forms. J Biol Chem. 2002;277:37184-90 pubmed publisher
    ..The high sequence identity, up to 60% between discriminating and nondiscriminating archaeal AspRSs, suggests that few mutational steps may be necessary to convert the tRNA-discriminating ability of a tRNA synthetase...
  18. Bernard D, Akochy P, Beaulieu D, Lapointe J, Roy P. Two residues in the anticodon recognition domain of the aspartyl-tRNA synthetase from Pseudomonas aeruginosa are individually implicated in the recognition of tRNAAsn. J Bacteriol. 2006;188:269-74 pubmed
    ..Therefore, these two determinants of specificity of P. aeruginosa AspRS could be important for all bacterial AspRSs. ..
  19. Suzuki K, Sato Y, Maeda Y, Shimizu S, Hossain M, Ubukata S, et al. Crystallization and preliminary X-ray crystallographic study of a putative aspartyl-tRNA synthetase from the crenarchaeon Sulfolobus tokodaii strain 7. Acta Crystallogr Sect F Struct Biol Cryst Commun. 2007;63:608-12 pubmed
    ..The structure has been successfully solved by the molecular-replacement method. Full refinement of the structure may reveal it to be the original ancestor of the nondiscriminating AspRS. ..
  20. Ruff M, Krishnaswamy S, Boeglin M, Poterszman A, Mitschler A, Podjarny A, et al. Class II aminoacyl transfer RNA synthetases: crystal structure of yeast aspartyl-tRNA synthetase complexed with tRNA(Asp). Science. 1991;252:1682-9 pubmed
    ..The conformation of the tRNA molecule in the complex is dictated more by the interaction with the protein than by its own sequence. ..
  21. Cirullo R, Arredondo Vega F, Smith M, Wasmuth J. Isolation and characterization of interspecific heat-resistant hybrids between a temperature-sensitive chinese hamster cell asparaginyl-tRNA synthetase mutant and normal human leukocytes: assignment of human asnS gene to chromosome 18. Somatic Cell Genet. 1983;9:215-33 pubmed
  22. Thompson D, Lazennec C, Plateau P, Simonson T. Probing electrostatic interactions and ligand binding in aspartyl-tRNA synthetase through site-directed mutagenesis and computer simulations. Proteins. 2008;71:1450-60 pubmed
    ..The data give insights into the complex electrostatic network in the AspRS active site and illustrate the difficulty in engineering charged-to-neutral changes of the preferred ligand. ..
  23. Sellami M, Fasiolo F, Dirheimer G, Ebel J, Gangloff J. Nucleotide sequence of the gene coding for yeast cytoplasmic aspartyl-tRNA synthetase (APS); mapping of the 5' and 3' termini of AspRS mRNA. Nucleic Acids Res. 1986;14:1657-66 pubmed
    ..The AspRS gene (APS) has a codon usage pattern typical of non abundant proteins. S1 nuclease analysis of APS mRNA showed a major start 17 bases downstream from a "TATA box" and stops near an RNA polymerase terminator sequence. ..
  24. Francklyn C. tRNA synthetase paralogs: evolutionary links in the transition from tRNA-dependent amino acid biosynthesis to de novo biosynthesis. Proc Natl Acad Sci U S A. 2003;100:9650-2 pubmed
  25. Aradjanski M, Doğan S, Lotter S, Wang S, Hermans S, Wibom R, et al. DARS2 protects against neuroinflammation and apoptotic neuronal loss, but is dispensable for myelin producing cells. Hum Mol Genet. 2017;26:4181-4189 pubmed publisher
    ..Remarkably, our results also suggest a role for early neuroinflammation in the disease progression, highlighting the possibility for therapeutic interventions of this process. ..
  26. Uluc K, Baskan O, Yildirim K, Ozsahin S, Koseoglu M, Isak B, et al. Leukoencephalopathy with brain stem and spinal cord involvement and high lactate: a genetically proven case with distinct MRI findings. J Neurol Sci. 2008;273:118-22 pubmed publisher
    ..In LBSL, distinct MRI findings should lead to the diagnosis, which can be confirmed by the analysis of the disease gene DARS2. ..
  27. Charron C, Roy H, Blaise M, Giege R, Kern D. Crystallization and preliminary X-ray diffraction data of an archaeal asparagine synthetase related to asparaginyl-tRNA synthetase. Acta Crystallogr D Biol Crystallogr. 2004;60:767-9 pubmed
    ..Two different native diffraction data sets were collected to 2.3 and 3.0 A resolution using synchrotron radiation and cryocooling for crystals belonging to space groups C2 and P2(1), respectively. ..
  28. Park S, Kim S, Choi H, Rhee Y, Lim S. Fibroblast growth factor 2-induced cytoplasmic asparaginyl-tRNA synthetase promotes survival of osteoblasts by regulating anti-apoptotic PI3K/Akt signaling. Bone. 2009;45:994-1003 pubmed publisher
    ..In conclusion, we suggest that NARS is one of the important mediators of FGF2 induced survival signaling in osteoblasts through the activation of PI3K/Akt survival pathway. ..
  29. Rees B, Webster G, Delarue M, Boeglin M, Moras D. Aspartyl tRNA-synthetase from Escherichia coli: flexibility and adaptability to the substrates. J Mol Biol. 2000;299:1157-64 pubmed
    ..In contrast to these induced-fit conformational changes, a few residues essential for the tRNA anticodon or aspartyl-adenylate recognition exist in a predefined conformation, ensured by specific interactions within the protein. ..
  30. Sharples G, Lloyd R. Location of a mutation in the aspartyl-tRNA synthetase gene of Escherichia coli K12. Mutat Res. 1991;264:93-6 pubmed
    ..3 kb from the 5' end of the ruvAB operon. A DNA fragment encoding the carboxy-terminus of AspRS was found to be sufficient to allow growth of a tls-1 strain at the non-permissive temperature. ..
  31. Salazar J, Zuniga R, Raczniak G, Becker H, Soll D, Orellana O. A dual-specific Glu-tRNA(Gln) and Asp-tRNA(Asn) amidotransferase is involved in decoding glutamine and asparagine codons in Acidithiobacillus ferrooxidans. FEBS Lett. 2001;500:129-31 pubmed
    ..These data suggest that the transamidation pathway is responsible for the formation of Gln-tRNA and Asn-tRNA in A. ferrooxidans. ..
  32. Anselme J, Hartlein M. Asparaginyl-tRNA synthetase from Escherichia coli has significant sequence homologies with yeast aspartyl-tRNA synthetase. Gene. 1989;84:481-5 pubmed
  33. Cardoso A, Polycarpo C, Martins O, Soll D. A non-discriminating aspartyl-tRNA synthetase from Halobacterium salinarum. RNA Biol. 2006;3:110-4 pubmed
    ..Thus, as was observed in an archaeal discriminating AspRS and a bacterial ND-AspRS, amino acids in these positions influence the enzyme's tRNA selection. ..
  34. Archontis G, Simonson T, Karplus M. Binding free energies and free energy components from molecular dynamics and Poisson-Boltzmann calculations. Application to amino acid recognition by aspartyl-tRNA synthetase. J Mol Biol. 2001;306:307-27 pubmed
    ..Finally, Asn binding to AspRS with neutral K198 or charged H449 is considered, and shown to be less favorable than with the charged K198 and neutral H449 used in the analysis. ..
  35. Zhu D, Lorber B, Sauter C, Ng J, Benas P, Le Grimellec C, et al. Growth kinetics, diffraction properties and effect of agarose on the stability of a novel crystal form of Thermus thermophilus aspartyl-tRNA synthetase-1. Acta Crystallogr D Biol Crystallogr. 2001;57:552-8 pubmed
    ..The growth mechanism of the novel crystals was monitored by atomic force microscopy. The gel stabilizes the crystal lattice under the cryogenic conditions used for structure determination at high resolution. ..
  36. Peeters N, Chapron A, Giritch A, Grandjean O, Lancelin D, Lhomme T, et al. Duplication and quadruplication of Arabidopsis thaliana cysteinyl- and asparaginyl-tRNA synthetase genes of organellar origin. J Mol Evol. 2000;50:413-23 pubmed
    ..These case histories are the best examples to date of capture of organellar aminoacyl-tRNA synthetases by the cytosolic protein synthesis machinery. ..
  37. Merritt E, Arakaki T, Larson E, Kelley A, Mueller N, Napuli A, et al. Crystal structure of the aspartyl-tRNA synthetase from Entamoeba histolytica. Mol Biochem Parasitol. 2010;169:95-100 pubmed publisher
    ..The E. histolytica AspRS structure shows a well-ordered N-terminus that contributes to the AspRS dimer interface. ..
  38. Novikova M, Kazakov T, Vondenhoff G, Semenova E, Rozenski J, Metlytskaya A, et al. MccE provides resistance to protein synthesis inhibitor microcin C by acetylating the processed form of the antibiotic. J Biol Chem. 2010;285:12662-9 pubmed publisher
    ..We speculate that MccE and related cellular acetyltransferases of the Rim family may detoxify various aminoacyl-nucleotides, either exogenous or those generated inside the cell. ..
  39. Min B, Kitabatake M, Polycarpo C, Pelaschier J, Raczniak G, Ruan B, et al. Protein synthesis in Escherichia coli with mischarged tRNA. J Bacteriol. 2003;185:3524-6 pubmed
    ..While large amounts of Asp-tRNA(Asn) are detrimental to E. coli, smaller amounts support protein synthesis and allow the formation of up to 38% of the wild-type level of missense-suppressed tryptophan synthetase. ..
  40. Tzoulis C, Schwarzlmüller T, Biermann M, Haugarvoll K, Bindoff L. Mitochondrial DNA homeostasis is essential for nigrostriatal integrity. Mitochondrion. 2016;28:33-7 pubmed publisher
    ..These results support the hypothesis that accumulating somatic mtDNA damage plays an important role in neurodegeneration. ..
  41. Cathopoulis T, Chuawong P, Hendrickson T. Novel tRNA aminoacylation mechanisms. Mol Biosyst. 2007;3:408-18 pubmed
    ..However, in some cases aaRSs with relaxed or novel substrate specificities cooperate with other enzymes to generate specific canonical and non-canonical aminoacyl-tRNAs. ..
  42. Archontis G, Simonson T. Dielectric relaxation in an enzyme active site: molecular dynamics simulations interpreted with a macroscopic continuum model. J Am Chem Soc. 2001;123:11047-56 pubmed
    ..This moderate value indicates that, for this system, the local protein polarizability in the active site is within at most a factor of 2 of that expected at nonspecific positions in a protein interior. ..
  43. Giege R, Florentz C, Kern D, Gangloff J, Eriani G, Moras D. Aspartate identity of transfer RNAs. Biochimie. 1996;78:605-23 pubmed
    ..Efficient aspartylation of minihelices is explained by the primordial role of G73. From this and other considerations it is suggested that aspartate identity appeared early in the history of tRNA aminoacylation systems. ..
  44. Perret V, Garcia A, Grosjean H, Ebel J, Florentz C, Giege R. Relaxation of a transfer RNA specificity by removal of modified nucleotides. Nature. 1990;344:787-9 pubmed
    ..Our results indicate that post-transcriptional modification of tRNAs introduces structural 'anti-determinants', restricting the efficiency with which the tRNAs are charged with inappropriate amino acids. ..
  45. Feng L, Yuan J, Toogood H, Tumbula Hansen D, Soll D. Aspartyl-tRNA synthetase requires a conserved proline in the anticodon-binding loop for tRNA(Asn) recognition in vivo. J Biol Chem. 2005;280:20638-41 pubmed
    ..radiodurans AspRS2 enzymes still capable of forming Asp-tRNA(Asp) but unable to recognize tRNA(Asn). This strongly suggests that proline 77 is responsible for the non-discriminatory tRNA recognition properties of this enzyme. ..
  46. Park S, Choi E, Kim S. Aminoacyl-tRNA synthetase-interacting multifunctional proteins (AIMPs): a triad for cellular homeostasis. IUBMB Life. 2010;62:296-302 pubmed publisher
    ..In this article, the roles of three nonenzymatic components of the multi-tRNA synthetase complex in the assembly of the components and in cell regulation are addressed. ..
  47. Jakubowski H. Aminoacyl thioester chemistry of class II aminoacyl-tRNA synthetases. Biochemistry. 1997;36:11077-85 pubmed
    ..That the thiol-binding subsite exists also in AspRS and SerRS, which do not need editing function, suggests that these class II enzymes possess vestigial editing functions. ..
  48. Fröhlich D, Suchowerska A, Spencer Z, von Jonquieres G, Klugmann C, Bongers A, et al. In vivocharacterization of the aspartyl-tRNA synthetase DARS: Homing in on the leukodystrophy HBSL. Neurobiol Dis. 2017;97:24-35 pubmed publisher
    ..In summary, our data is an important contribution to a better understanding of DARS function and HBSL pathology. ..
  49. Ramirez B, Howard O, Dong H, Edamatsu T, Gao P, Hartlein M, et al. Brugia malayi asparaginyl-transfer RNA synthetase induces chemotaxis of human leukocytes and activates G-protein-coupled receptors CXCR1 and CXCR2. J Infect Dis. 2006;193:1164-71 pubmed
    ..Our findings suggest that a filarial parasite chemoattractant protein may contribute to the development of chronic inflammatory disease and that chemokine receptors may be therapeutic targets to ameliorate parasite-induced pathology. ..
  50. Becker H, Roy H, Moulinier L, Mazauric M, Keith G, Kern D. Thermus thermophilus contains an eubacterial and an archaebacterial aspartyl-tRNA synthetase. Biochemistry. 2000;39:3216-30 pubmed
    ..thermophilus to eubacteria and archaebacteria...
  51. Pletzer D, Braun Y, Dubiley S, Lafon C, Köhler T, Page M, et al. The Pseudomonas aeruginosa PA14 ABC Transporter NppA1A2BCD Is Required for Uptake of Peptidyl Nucleoside Antibiotics. J Bacteriol. 2015;197:2217-2228 pubmed publisher
    ..In this study, we analyzed an ABC transporter involved in the uptake of nucleoside peptidyl antibiotics. Our data might help to design drug conjugates that may hijack this uptake system to gain access to cells. ..
  52. Anselme J, Hartlein M. Tyr-426 of the Escherichia coli asparaginyl-tRNA synthetase, an amino acid in a C-terminal conserved motif, is involved in ATP binding. FEBS Lett. 1991;280:163-6 pubmed
    ..The replacement of this Tyr-426 by a Phe does not affect the kinetic behaviour of the enzyme. These data indicate that Tyr-426 is part of the ATP binding site. ..
  53. Hirakata M, Suwa A, Nagai S, Kron M, Trieu E, Mimori T, et al. Anti-KS: identification of autoantibodies to asparaginyl-transfer RNA synthetase associated with interstitial lung disease. J Immunol. 1999;162:2315-20 pubmed
    ..Anti-KS was more closely associated with ILD than with myositis. Further study of this Abs might prove useful in dissecting the stimuli responsible for the genesis of anti-synthetase autoantibodies. ..