glycine trna ligase

Summary

Summary: An enzyme that activates glycine with its specific transfer RNA. EC 6.1.1.14.

Top Publications

  1. Adrian Scotto M, Vasilescu D. Quantum molecular modeling of glycyl-adenylate. J Biomol Struct Dyn. 2008;25:697-708 pubmed
  2. Antonellis A, Ellsworth R, Sambuughin N, Puls I, Abel A, Lee Lin S, et al. Glycyl tRNA synthetase mutations in Charcot-Marie-Tooth disease type 2D and distal spinal muscular atrophy type V. Am J Hum Genet. 2003;72:1293-9 pubmed
    ..This is the first example of an aminoacyl tRNA synthetase being implicated in a human genetic disease, which makes genes that encode these enzymes relevant candidates for other inherited neuropathies and motor neuron diseases. ..
  3. Del Bo R, Locatelli F, Corti S, Scarlato M, Ghezzi S, Prelle A, et al. Coexistence of CMT-2D and distal SMA-V phenotypes in an Italian family with a GARS gene mutation. Neurology. 2006;66:752-4 pubmed
    ..A novel heterozygous missense GARS gene mutation (D500N) was identified. ..
  4. Sivakumar K, Kyriakides T, Puls I, Nicholson G, Funalot B, Antonellis A, et al. Phenotypic spectrum of disorders associated with glycyl-tRNA synthetase mutations. Brain. 2005;128:2304-14 pubmed
    ..Awareness of these overlapping clinical phenotypes associated with mutations in GARS will facilitate identification of this disorder in additional families and direct future research toward better understanding of its pathogenesis. ..
  5. Dubourg O, Azzedine H, Yaou R, Pouget J, Barois A, Meininger V, et al. The G526R glycyl-tRNA synthetase gene mutation in distal hereditary motor neuropathy type V. Neurology. 2006;66:1721-6 pubmed
    ..Glycyl-tRNA synthetase mutations are a frequent cause of familial distal hereditary motor neuropathy type V but, because of the reduced penetrance of the disease, could also account for isolated cases. ..
  6. James P, Cader M, Muntoni F, Childs A, Crow Y, Talbot K. Severe childhood SMA and axonal CMT due to anticodon binding domain mutations in the GARS gene. Neurology. 2006;67:1710-2 pubmed
    ..One mutation was in the anticodon binding domain and associated with onset in early childhood and predominant involvement of the lower limbs, thus extending the phenotype associated with GARS mutations. ..
  7. Wolf Y, Koonin E. Origin of an animal mitochondrial DNA polymerase subunit via lineage-specific acquisition of a glycyl-tRNA synthetase from bacteria of the Thermus-Deinococcus group. Trends Genet. 2001;17:431-3 pubmed
  8. Rivas M, Seeger M, Jedlicki E, Holmes D. Second acyl homoserine lactone production system in the extreme acidophile Acidithiobacillus ferrooxidans. Appl Environ Microbiol. 2007;73:3225-31 pubmed
  9. Schneider T, Senn M, Berger B chi B, Tossi A, Sahl H, Wiedemann I. In vitro assembly of a complete, pentaglycine interpeptide bridge containing cell wall precursor (lipid II-Gly5) of Staphylococcus aureus. Mol Microbiol. 2004;53:675-85 pubmed publisher
    ..The in vitro assembly system described here will enable detailed analysis of late, membrane-associated steps of S. aureus peptidoglycan biosynthesis...

More Information

Publications62

  1. Samuelsson T, Boren T, Johansen T, Lustig F. Properties of a transfer RNA lacking modified nucleosides. J Biol Chem. 1988;263:13692-9 pubmed
  2. Deng X, Qin X, Chen L, Jia Q, Zhang Y, Zhang Z, et al. Large Conformational Changes of Insertion 3 in Human Glycyl-tRNA Synthetase (hGlyRS) during Catalysis. J Biol Chem. 2016;291:5740-52 pubmed publisher
    ..The biophysical and biochemical studies suggest that human GlyRS may utilize its flexibility for both the traditional function (regulate tRNA binding) and alternative functions (roles in diseases). ..
  3. Nameki N, Tamura K, Asahara H, Hasegawa T. Recognition of tRNA(Gly) by three widely diverged glycyl-tRNA synthetases. J Mol Biol. 1997;268:640-7 pubmed
    ..The clear separation between prokaryotes and yeast is retained in the identity element location, whereas the apparent diversity of the two prokaryotic enzymes does not reflect on the tRNA recognition. ..
  4. Nagel G, Johnson M, Rynd J, Petrella E, Weber B. Glycyl-tRNA synthetase of Escherichia coli: immunological homology with phenylalanyl-tRNA synthetase. Arch Biochem Biophys. 1988;262:409-15 pubmed
    ..In contrast, GlyRS antibodies did not cross-react with a number of other aminoacyl-tRNA synthetase activities from E. coli, yeast, or Bacillus. ..
  5. Hipps D, Shiba K, Henderson B, Schimmel P. Operational RNA code for amino acids: species-specific aminoacylation of minihelices switched by a single nucleotide. Proc Natl Acad Sci U S A. 1995;92:5550-2 pubmed
    ..Thus, the positional locations (if not the actual nucleotides) for the operational RNA code for glycine appear conserved from bacteria to mammals. ..
  6. McDonald T, Breite L, Pangburn K, Hom S, Manser J, Nagel G. Overproduction, purification, and subunit structure of Escherichia coli glycyl transfer ribonucleic acid synthetase. Biochemistry. 1980;19:1402-9 pubmed
  7. Claesson C, Samuelsson T, Lustig F, Boren T. Codon reading properties of an unmodified transfer RNA. FEBS Lett. 1990;273:173-6 pubmed
  8. Mo Z, Zhang Q, Liu Z, Lauer J, Shi Y, Sun L, et al. Neddylation requires glycyl-tRNA synthetase to protect activated E2. Nat Struct Mol Biol. 2016;23:730-7 pubmed publisher
    ..Therefore, GlyRS functions as a chaperone that critically supports neddylation. This function is probably conserved in all eukaryotic GlyRS enzymes and may contribute to the strong association of GlyRS with cancer progression. ..
  9. Valencia Sánchez M, Rodríguez Hernández A, Ferreira R, Santamaría Suárez H, Arciniega M, Dock Bregeon A, et al. Structural Insights into the Polyphyletic Origins of Glycyl tRNA Synthetases. J Biol Chem. 2016;291:14430-46 pubmed publisher
  10. Seburn K, Nangle L, Cox G, Schimmel P, Burgess R. An active dominant mutation of glycyl-tRNA synthetase causes neuropathy in a Charcot-Marie-Tooth 2D mouse model. Neuron. 2006;51:715-26 pubmed
  11. Francklyn C, Shi J, Schimmel P. Overlapping nucleotide determinants for specific aminoacylation of RNA microhelices. Science. 1992;255:1121-5 pubmed
    ..An analysis of the relative contributions of these microhelices to overall tRNA recognition indicated that their interaction with aaRSs constitutes a substantial part of the recognition of the whole tRNAs. ..
  12. Duchêne A, Peeters N, Dietrich A, Cosset A, Small I, Wintz H. Overlapping destinations for two dual targeted glycyl-tRNA synthetases in Arabidopsis thaliana and Phaseolus vulgaris. J Biol Chem. 2001;276:15275-83 pubmed
    ..Unexpectedly, GlyRS-1 seems to be active in the cytosol but inactive in mitochondrial fractions, whereas GlyRS-2 is likely to glycylate both the organelle-encoded tRNA(Gly) and the imported tRNA(Gly) present in mitochondria. ..
  13. Toth M, Schimmel P. Internal structural features of E. coli glycyl-tRNA synthetase examined by subunit polypeptide chain fusions. J Biol Chem. 1986;261:6643-6 pubmed
  14. Xie W, Nangle L, Zhang W, Schimmel P, Yang X. Long-range structural effects of a Charcot-Marie-Tooth disease-causing mutation in human glycyl-tRNA synthetase. Proc Natl Acad Sci U S A. 2007;104:9976-81 pubmed
    ..From analysis of a third crystal, an appended motif, found in higher eukaryote GlyRSs, seems not to have a role in these long-range effects. ..
  15. Chihara T, Luginbuhl D, Luo L. Cytoplasmic and mitochondrial protein translation in axonal and dendritic terminal arborization. Nat Neurosci. 2007;10:828-37 pubmed
    ..Our study highlights different demands of protein translation for the development and maintenance of axons and dendrites. ..
  16. Sun A, Liu X, Zheng M, Sun Q, Huang Y, Fan D. A novel mutation of the glycyl-tRNA synthetase (GARS) gene associated with Charcot-Marie-Tooth type 2D in a Chinese family. Neurol Res. 2015;37:782-7 pubmed publisher
    ..999G>T (p.E333D), of the GARS gene. The c.999G>T mutation is a novel mutation of the GARS gene that has not been previously reported. The phenotype of this family is CMT2D, which is first reported in Chinese population. ..
  17. Gerard H, Whittum Hudson J, Hudson A. Genes required for assembly and function of the protein synthetic system in Chlamydia trachomatis are expressed early in elementary to reticulate body transformation. Mol Gen Genet. 1997;255:637-42 pubmed
    ..Thus, expression of bacterial genes whose products are required for protein synthesis begins earlier in chlamydial EB to RB development than previously thought. ..
  18. Cader M, Ren J, James P, Bird L, Talbot K, Stammers D. Crystal structure of human wildtype and S581L-mutant glycyl-tRNA synthetase, an enzyme underlying distal spinal muscular atrophy. FEBS Lett. 2007;581:2959-64 pubmed
    ..Reduced enzyme activity may underlie neuronal degeneration, although a dominant-negative effect is more likely in this autosomal dominant disorder. ..
  19. Williams J, Osvath S, Khong T, Pearse M, Power D. Cloning, sequencing and bacterial expression of human glycine tRNA synthetase. Nucleic Acids Res. 1995;23:1307-10 pubmed
    ..Bacterial extract containing the fusion protein catalyses the aminoacylation of bovine tRNA with [14C]-gly at 10-fold increased level above normal bacterial extract and confirms that the cDNA encodes human GlyRS. ..
  20. Grundy F, Yousef M, Henkin T. Monitoring uncharged tRNA during transcription of the Bacillus subtilis glyQS gene. J Mol Biol. 2005;346:73-81 pubmed
    ..These results suggest that the transcription complex can interact with either uncharged or charged tRNA until it approaches the termination point, allowing maximal flexibility in monitoring the ratio of charged to uncharged tRNA. ..
  21. Dignam J, Nada S, Chaires J. Thermodynamic characterization of the binding of nucleotides to glycyl-tRNA synthetase. Biochemistry. 2003;42:5333-40 pubmed
    ..The results are consistent with a significant conformational transition in glycyl-tRNA synthetase coupled to the binding of GSAd. ..
  22. Magrath C, Hyman L. A mutation in GRS1, a glycyl-tRNA synthetase, affects 3'-end formation in Saccharomyces cerevisiae. Genetics. 1999;152:129-41 pubmed
    ..On the basis of our results, we suggest Grs1p is a transcription termination factor that may interact with the 3'-end of pre-mRNA to promote 3'-end formation. ..
  23. Apostolidi M, Saad N, Drainas D, Pournaras S, Becker H, Stathopoulos C. A glyS T-box riboswitch with species-specific structural features responding to both proteinogenic and nonproteinogenic tRNAGly isoacceptors. RNA. 2015;21:1790-806 pubmed publisher
    ..aureus glyS T-box exhibits differential tRNA selectivity, which possibly contributes toward the regulation and synchronization of ribosomal and exoribosomal peptide synthesis, two essential but metabolically unrelated pathways. ..
  24. Diaz Lazcoz Y, Aude J, Nitschke P, Chiapello H, Landès Devauchelle C, Risler J. Evolution of genes, evolution of species: the case of aminoacyl-tRNA synthetases. Mol Biol Evol. 1998;15:1548-61 pubmed
    ..Thus, aaRS's are clearly a paradigm of F. Jacob's "odd jobs of evolution" but, on the whole, do not call into question the evolutionary scenario originally proposed by Woese and subsequently refined by others. ..
  25. Chang C, Chien C, Chang C, Lin B, Wang C. A WHEP Domain Regulates the Dynamic Structure and Activity of Caenorhabditis elegans Glycyl-tRNA Synthetase. J Biol Chem. 2016;291:16567-75 pubmed publisher
    ..Most interestingly, the deletion mutant possessed a higher thermal stability and a somewhat lower structural flexibility. Our study suggests a role for the WHEP domain as a regulator of the dynamic structure and activity of the enzyme. ..
  26. Turner R, Lovato M, Schimmel P. One of two genes encoding glycyl-tRNA synthetase in Saccharomyces cerevisiae provides mitochondrial and cytoplasmic functions. J Biol Chem. 2000;275:27681-8 pubmed
    ..Phylogenetic analysis shows that GlyRS2 is a predecessor of all yeast GlyRS homologues. Thus, GRS1 appears to be the result of a duplication of GRS2, which itself is pseudogene-like. ..
  27. Griffin L, Sakaguchi R, McGuigan D, Gonzalez M, Searby C, Züchner S, et al. Impaired function is a common feature of neuropathy-associated glycyl-tRNA synthetase mutations. Hum Mutat. 2014;35:1363-71 pubmed publisher
    ..Together, our data indicate that impaired function is a key component of GARS-mediated CMT disease and emphasize the need for careful genetic and functional evaluation before implicating a variant in disease onset. ..
  28. Candeliere G, Rao Y, Floh A, Sandler S, Aubin J. cDNA fingerprinting of osteoprogenitor cells to isolate differentiation stage-specific genes. Nucleic Acids Res. 1999;27:1079-83 pubmed
    ..This method offers a functional genomics approach to isolate differentiation stage-specific genes in samples as small as a single cell. ..
  29. Keng T, Schimmel P. Synthesis of two polypeptide subunits of an aminoacyl tRNA synthetase as a single polypeptide chain. J Biomol Struct Dyn. 1983;1:225-9 pubmed
    ..This shows that the fusion protein is stable in vivo and suggests that Gly-tRNA synthetase is operationally a single polypeptide which is the ancestor of the two subunits. ..
  30. Nangle L, Zhang W, Xie W, Yang X, Schimmel P. Charcot-Marie-Tooth disease-associated mutant tRNA synthetases linked to altered dimer interface and neurite distribution defect. Proc Natl Acad Sci U S A. 2007;104:11239-44 pubmed
    ..In contrast, all mutant proteins were distribution-defective. Thus, CMT-causing mutations of GlyRS share a common defect in localization. This defect may be connected in some way to a change in the surfaces at the dimer interface. ..
  31. Scherer S. Inherited neuropathies: new genes don't fit old models. Neuron. 2006;51:672-4 pubmed
    ..In this issue of Neuron, Seburn et al. have identified and characterized a mutant mouse with a dominantly inherited axonal neuropathy caused by a Gars mutation that is inferred to have a gain of function. ..
  32. Mazauric M, Keith G, Logan D, Kreutzer R, Gieg R, Kern D. Glycyl-tRNA synthetase from Thermus thermophilus--wide structural divergence with other prokaryotic glycyl-tRNA synthetases and functional inter-relation with prokaryotic and eukaryotic glycylation systems. Eur J Biochem. 1998;251:744-57 pubmed
    ..These features are discussed in the context of the phylogenic connections between prokaryotes, eukaryotes, and archaebacteria, and of the particular place of T. thermophilus in this phylogeny...
  33. Logan D, Mazauric M, Kern D, Moras D. Crystal structure of glycyl-tRNA synthetase from Thermus thermophilus. EMBO J. 1995;14:4156-67 pubmed
    ..The active site residues most probably responsible for substrate recognition, in particular in the Gly binding pocket, can be identified by inference from aspartyl-tRNA synthetase due to the conserved nature of the class II active site. ..
  34. Nagel G, Cumberledge S, Johnson M, Petrella E, Weber B. The beta subunit of E. coli glycyl-tRNA synthetase plays a major role in tRNA recognition. Nucleic Acids Res. 1984;12:4377-84 pubmed
    ..Taken together, the data indicate that the larger, beta subunit of glycyl-tRNA synthetase plays a major role in tRNA recognition. ..
  35. Johanson K, Hoang T, Sheth M, Hyman L. GRS1, a yeast tRNA synthetase with a role in mRNA 3' end formation. J Biol Chem. 2003;278:35923-30 pubmed
    ..These results establish a direct role for GRS1 in mRNA 3' end formation. ..
  36. Chang K, Wang C. Translation initiation from a naturally occurring non-AUG codon in Saccharomyces cerevisiae. J Biol Chem. 2004;279:13778-85 pubmed
    ..The results suggest that non-AUG initiation might be a mechanism existing throughout all kingdoms. ..
  37. Guo R, Chong Y, Guo M, Yang X. Crystal structures and biochemical analyses suggest a unique mechanism and role for human glycyl-tRNA synthetase in Ap4A homeostasis. J Biol Chem. 2009;284:28968-76 pubmed publisher
    ..A special role for GlyRS in Ap4A homeostasis is proposed. ..
  38. Targoff I, Trieu E, Plotz P, Miller F. Antibodies to glycyl-transfer RNA synthetase in patients with myositis and interstitial lung disease. Arthritis Rheum. 1992;35:821-30 pubmed
    ..The finding of specific inhibition of gly-tRNA synthetase by all anti-EJ-positive sera strongly supports the identification of EJ antigen as gly-tRNA synthetase. ..
  39. Logan D, Cura V, Touzel J, Kern D, Moras D. Crystallisation of the glycyl-tRNA synthetase from Thermus thermophilus and initial crystallographic data. J Mol Biol. 1994;241:732-5 pubmed publisher
    ..The best native data extend to 2.9 A in C2,2,2(1) and are 90.6% complete with an R-factor between symmetry-related reflections of 10.0%. The structure has been solved by multiple isomorphous replacement and model building is in progress...
  40. Forster C, Zerressen Harte A, Fürste J, Perbandt M, Betzel C, Erdmann V. Comparative X-ray structure analysis of human and Escherichia coli tRNA(Gly) acceptor stem microhelices. Biochem Biophys Res Commun. 2008;368:1002-6 pubmed publisher
    ..In this study, we present a comparison between the crystal structures of the eubacterial Escherichia coli and the human tRNA(Gly) acceptor stem microhelices and their surrounding hydration patterns. ..
  41. He W, Bai G, Zhou H, Wei N, White N, Lauer J, et al. CMT2D neuropathy is linked to the neomorphic binding activity of glycyl-tRNA synthetase. Nature. 2015;526:710-4 pubmed publisher
  42. Toth M, Schimmel P. A mutation in the small (alpha) subunit of glycyl-tRNA synthetase affects amino acid activation and subunit association parameters. J Biol Chem. 1990;265:1005-9 pubmed
    ..The results of this study suggest that the alpha chain specifically contributes to amino acid and to ATP binding in a way that is affected by proper subunit interactions. ..
  43. Abe A, Hayasaka K. The GARS gene is rarely mutated in Japanese patients with Charcot-Marie-Tooth neuropathy. J Hum Genet. 2009;54:310-2 pubmed publisher
    ..893C>T) mutation in a patient showing adolescent onset and early upper limb involvement. Results of our study indicate that GARS mutation is a rare cause of CMT2 among Japanese patients. ..
  44. Bais P, Beebe K, Morelli K, Currie M, Norberg S, Evsikov A, et al. Metabolite profile of a mouse model of Charcot-Marie-Tooth type 2D neuropathy: implications for disease mechanisms and interventions. Biol Open. 2016;5:908-20 pubmed publisher
  45. Arnez J, Dock Bregeon A, Moras D. Glycyl-tRNA synthetase uses a negatively charged pit for specific recognition and activation of glycine. J Mol Biol. 1999;286:1449-59 pubmed
    ..On the basis of this similarity, we propose that GlyRS utilizes the same general mechanism as that employed by other class II aminoacyl-tRNA synthetases. ..
  46. Mudge S, Williams J, Eyre H, Sutherland G, Cowan P, Power D. Complex organisation of the 5'-end of the human glycine tRNA synthetase gene. Gene. 1998;209:45-50 pubmed
    ..9 kb genomic fragment containing the TSP and TATA box, but by a contiguous 0.4 kb fragment immediately downstream. These studies suggest that the transcription of glyRS from a single start point requires downstream promoter elements. ..
  47. Viswanathan S, Dignam S, Dignam J. Control of the levels of alanyl-, glycyl-, and seryl-tRNA synthetases in the silkgland of Bombyx mori. Dev Biol. 1988;129:350-7 pubmed
    ..A form of alanyl-tRNA synthetase with a slightly higher apparent molecular weight is detected in the posterior silkgland early in the fifth instar and in ovarian tissue. ..
  48. Wu H, Nada S, Dignam J. Analysis of truncated forms of Bombyx mori glycyl-tRNA synthetase: function of an N-terminal structure in RNA binding. Biochemistry. 1995;34:16327-36 pubmed
    ..The first 55 N-terminal residues are not essential for catalysis, dimerization, or substrate binding in aminoacylation but are required for RNA binding not associated with aminoacylation. ..
  49. Keng T, Webster T, Sauer R, Schimmel P. Gene for Escherichia coli glycyl-tRNA synthetase has tandem subunit coding regions in the same reading frame. J Biol Chem. 1982;257:12503-8 pubmed
  50. Benoy V, Van Helleputte L, Prior R, d Ydewalle C, Haeck W, Geens N, et al. HDAC6 is a therapeutic target in mutant GARS-induced Charcot-Marie-Tooth disease. Brain. 2018;141:673-687 pubmed publisher
  51. Scandurro A, Weldon C, Figueroa Y, Alam J, Beckman B. Gene microarray analysis reveals a novel hypoxia signal transduction pathway in human hepatocellular carcinoma cells. Int J Oncol. 2001;19:129-35 pubmed
    ..These findings were all corroborated by RT-PCR assays and in some instances Western blot analysis. ..
  52. Hu J, Tian J, Li F, Xue B, Hu J, Cheng X, et al. Clone and functional analysis of Seryl-tRNA synthetase and Tyrosyl-tRNA synthetase from silkworm, Bombyx mori. Sci Rep. 2017;7:41563 pubmed publisher
  53. Alexandrova J, Paulus C, Rudinger Thirion J, Jossinet F, Frugier M. Elaborate uORF/IRES features control expression and localization of human glycyl-tRNA synthetase. RNA Biol. 2015;12:1301-13 pubmed publisher
    ..This finding reveals a complex picture of GARS translation and localization in mammals. In this context, we discuss how human GARS expression could influence its moonlighting activities and its involvement in diseases. ..