nitrogenous group transferases


Summary: Enzymes that catalyze the transfer of nitrogenous groups, primarily amino groups, from a donor, generally an amino acid, to an acceptor, usually a 2-oxoacid. EC 2.6.

Top Publications

  1. Deniziak M, Sauter C, Becker H, Paulus C, Gieg R, Kern D. Deinococcus glutaminyl-tRNA synthetase is a chimer between proteins from an ancient and the modern pathways of aminoacyl-tRNA formation. Nucleic Acids Res. 2007;35:1421-31 pubmed publisher
    ..However, the presence of Yqey in free state in organisms lacking GlnRS, suggests that this domain may exert additional cellular functions...
  2. Sheppard K, Yuan J, Hohn M, Jester B, Devine K, Soll D. From one amino acid to another: tRNA-dependent amino acid biosynthesis. Nucleic Acids Res. 2008;36:1813-25 pubmed publisher
    ..How these tRNA-dependent amino acid biosynthetic routes are integrated into overall metabolism may explain why they are still retained in so many organisms. ..
  3. Curnow A, Tumbula D, Pelaschier J, Min B, Soll D. Glutamyl-tRNA(Gln) amidotransferase in Deinococcus radiodurans may be confined to asparagine biosynthesis. Proc Natl Acad Sci U S A. 1998;95:12838-43 pubmed
    ..radiodurans extracts, suggests that the gatCAB genes may be responsible for biosynthesis of asparagine in this asparagine prototroph. ..
  4. Ito T, Yokoyama S. Two enzymes bound to one transfer RNA assume alternative conformations for consecutive reactions. Nature. 2010;467:612-6 pubmed publisher
    ..The proposed mechanism explains how the transamidosome efficiently performs the two consecutive steps of Gln-tRNA(Gln) formation, with a low risk of releasing the unstable intermediate Glu-tRNA(Gln). ..
  5. Becker H, Min B, Jacobi C, Raczniak G, Pelaschier J, Roy H, et al. The heterotrimeric Thermus thermophilus Asp-tRNA(Asn) amidotransferase can also generate Gln-tRNA(Gln). FEBS Lett. 2000;476:140-4 pubmed
  6. Huot J, Fischer F, Corbeil J, Madore E, Lorber B, Diss G, et al. Gln-tRNAGln synthesis in a dynamic transamidosome from Helicobacter pylori, where GluRS2 hydrolyzes excess Glu-tRNAGln. Nucleic Acids Res. 2011;39:9306-15 pubmed publisher
  7. Barros M, Rak M, Paulela J, Tzagoloff A. Characterization of Gtf1p, the connector subunit of yeast mitochondrial tRNA-dependent amidotransferase. J Biol Chem. 2011;286:32937-47 pubmed publisher
    ..Senger, B., Brayé, M., Kern, D., Martin, R. P., and Becker, H. D. (2009) Genes Dev. 23, 1119-1130). ..
  8. Harpel M, Horiuchi K, Luo Y, Shen L, Jiang W, Nelson D, et al. Mutagenesis and mechanism-based inhibition of Streptococcus pyogenes Glu-tRNAGln amidotransferase implicate a serine-based glutaminase site. Biochemistry. 2002;41:6398-407 pubmed
  9. Leuendorf J, Osorio S, Szewczyk A, Fernie A, Hellmann H. Complex assembly and metabolic profiling of Arabidopsis thaliana plants overexpressing vitamin B? biosynthesis proteins. Mol Plant. 2010;3:890-903 pubmed publisher
    ..3. These findings provide first insights into in planta vitamin B? synthase complex assembly and new information on how the different PDX proteins affect plant metabolism. ..

More Information


  1. Oshikane H, Sheppard K, Fukai S, Nakamura Y, Ishitani R, Numata T, et al. Structural basis of RNA-dependent recruitment of glutamine to the genetic code. Science. 2006;312:1950-4 pubmed publisher
    ..tRNA(Gln) recognition by indirect readout based on shape complementarity of the D loop suggests an early anticodon-independent RNA-based mechanism for adding glutamine to the genetic code...
  2. Wagner S, Bernhardt A, Leuendorf J, Drewke C, Lytovchenko A, Mujahed N, et al. Analysis of the Arabidopsis rsr4-1/pdx1-3 mutant reveals the critical function of the PDX1 protein family in metabolism, development, and vitamin B6 biosynthesis. Plant Cell. 2006;18:1722-35 pubmed
    ..In summary, our results demonstrate the critical function of the PDX1 protein family for metabolism, whole-plant development, and vitamin B6 biosynthesis in higher plants. ..
  3. Tambasco Studart M, Titiz O, Raschle T, Forster G, Amrhein N, Fitzpatrick T. Vitamin B6 biosynthesis in higher plants. Proc Natl Acad Sci U S A. 2005;102:13687-92 pubmed
    ..Furthermore, and contrary to what was inferred previously, we show that the pathway appears to be cytosolic and is not localized to the plastid. Last, we report that the single PDX2 homolog is essential for plant viability. ..
  4. Biarrotte Sorin S, Maillard A, Delettré J, Sougakoff W, Arthur M, Mayer C. Crystal structures of Weissella viridescens FemX and its complex with UDP-MurNAc-pentapeptide: insights into FemABX family substrates recognition. Structure. 2004;12:257-67 pubmed
  5. Hegde S, Blanchard J. Kinetic and mechanistic characterization of recombinant Lactobacillus viridescens FemX (UDP-N-acetylmuramoyl pentapeptide-lysine N6-alanyltransferase). J Biol Chem. 2003;278:22861-7 pubmed
    ..Site-directed mutagenesis identified Asp109 as a candidate for the catalytic base and Glu320 plays an additional important role in the catalytic function of the enzyme. ..
  6. Wu J, Bu W, Sheppard K, Kitabatake M, Kwon S, Soll D, et al. Insights into tRNA-dependent amidotransferase evolution and catalysis from the structure of the Aquifex aeolicus enzyme. J Mol Biol. 2009;391:703-16 pubmed publisher
    ..aeolicus GatB. The two sites enable GatCAB to first phosphorylate the misacylated tRNA substrate and then amidate the activated intermediate to form the cognate products, Gln-tRNA(Gln) or Asn-tRNA(Asn). ..
  7. Zhao L, Dewage S, Bell M, Chang K, Fatma S, Joshi N, et al. The kinase activity of the Helicobacter pylori Asp-tRNA(Asn)/Glu-tRNA(Gln) amidotransferase is sensitive to distal mutations in its putative ammonia tunnel. Biochemistry. 2012;51:273-85 pubmed publisher
    ..A comparison of wild-type, T149V, and K89R AdT simulation results unmasks 59 common residues that are likely involved in connecting the two active sites. ..
  8. Curnow A, Hong K, Yuan R, Kim S, Martins O, Winkler W, et al. Glu-tRNAGln amidotransferase: a novel heterotrimeric enzyme required for correct decoding of glutamine codons during translation. Proc Natl Acad Sci U S A. 1997;94:11819-26 pubmed
    ..Disruption of this operon is lethal. This demonstrates that transamidation is the only pathway to Gln-tRNAGln in B. subtilis and that glutamyl-tRNAGln amidotransferase is a novel and essential component of the translational apparatus. ..
  9. Rampias T, Sheppard K, Soll D. The archaeal transamidosome for RNA-dependent glutamine biosynthesis. Nucleic Acids Res. 2010;38:5774-83 pubmed publisher
    ..The differences between the two transamidosomes may be a consequence of the fact that ND-GluRS is a class I aminoacyl-tRNA synthetase, while ND-AspRS belongs to the class II family. ..
  10. 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. ..
  11. Sheppard K, Sherrer R, Soll D. Methanothermobacter thermautotrophicus tRNA Gln confines the amidotransferase GatCAB to asparaginyl-tRNA Asn formation. J Mol Biol. 2008;377:845-53 pubmed publisher
    ..pylori or B. subtilis, and M. thermautotrophicus Glu-tRNA(Asn). Thus, M. thermautotrophicus encodes two amidotransferases, each with its own activity, GatDE for Gln-tRNA and GatCAB for Asn-tRNA synthesis. ..
  12. Pujol C, Bailly M, Kern D, Maréchal Drouard L, Becker H, Duchene A. Dual-targeted tRNA-dependent amidotransferase ensures both mitochondrial and chloroplastic Gln-tRNAGln synthesis in plants. Proc Natl Acad Sci U S A. 2008;105:6481-5 pubmed publisher
    ..Moreover, the mitochondrial pathway of Gln-tRNA(Gln) formation is shared with chloroplasts as both the GluRS, and the three AdT subunits are dual-imported into mitochondria and chloroplasts. ..
  13. Baick J, Yoon J, Namgoong S, Soll D, Kim S, Eom S, et al. Growth inhibition of Escherichia coli during heterologous expression of Bacillus subtilis glutamyl-tRNA synthetase that catalyzes the formation of mischarged glutamyl-tRNA1 Gln. J Microbiol. 2004;42:111-6 pubmed
    ..coli GlutRNA1 Gln, and converts it to the cognate Gln-tRNA1 Gln species. B. subtilis GluRS-dependent Glu-tRNA1 Gln formation may cause growth inhibition in the transformed E. coli strain, possibly due to abnormal protein synthesis. ..
  14. Denslow S, Rueschhoff E, Daub M. Regulation of the Arabidopsis thaliana vitamin B6 biosynthesis genes by abiotic stress. Plant Physiol Biochem. 2007;45:152-61 pubmed
    ..Insight into regulation of the biosynthetic genes during abiotic stress could have important applications in the development of stress-tolerant crops. ..
  15. Nakamura A, Sheppard K, Yamane J, Yao M, Soll D, Tanaka I. Two distinct regions in Staphylococcus aureus GatCAB guarantee accurate tRNA recognition. Nucleic Acids Res. 2010;38:672-82 pubmed publisher
  16. Schmitt E, Panvert M, Blanquet S, Mechulam Y. Structural basis for tRNA-dependent amidotransferase function. Structure. 2005;13:1421-33 pubmed publisher
    ..Comparison of GatD and L-asparaginase structures shows how the motion of a beta hairpin region containing a crucial catalytic threonine may control the overall reaction cycle of GatDE...
  17. Blaise M, Bailly M, Frechin M, Behrens M, Fischer F, Oliveira C, et al. Crystal structure of a transfer-ribonucleoprotein particle that promotes asparagine formation. EMBO J. 2010;29:3118-29 pubmed publisher
    ..The transamidosome constitutes a transfer-ribonucleoprotein particle in which tRNAs serve the function of both substrate and structural foundation for a large molecular machine...
  18. Strauch M, Zalkin H, Aronson A. Characterization of the glutamyl-tRNA(Gln)-to-glutaminyl-tRNA(Gln) amidotransferase reaction of Bacillus subtilis. J Bacteriol. 1988;170:916-20 pubmed
    ..In addition, there was no inhibition by inhibitors of either glutamine synthetase or other amidotransferases. A unique, rather labile activity seems to be required for this reaction...
  19. Bailly M, Blaise M, Roy H, Deniziak M, Lorber B, Birck C, et al. tRNA-dependent asparagine formation in prokaryotes: characterization, isolation and structural and functional analysis of a ribonucleoprotein particle generating Asn-tRNA(Asn). Methods. 2008;44:146-63 pubmed publisher
  20. Tambasco Studart M, Tews I, Amrhein N, Fitzpatrick T. Functional analysis of PDX2 from Arabidopsis, a glutaminase involved in vitamin B6 biosynthesis. Plant Physiol. 2007;144:915-25 pubmed
    ..Based on a model of the PDX1/PDX2 complex, mutation of a single residue uncouples enzyme coordination and in turn provides tangible evidence for the existence of the recently proposed ammonia tunnel through the core of PDX1. ..
  21. Chen H, Xiong L. Pyridoxine is required for post-embryonic root development and tolerance to osmotic and oxidative stresses. Plant J. 2005;44:396-408 pubmed
    ..Our study establishes a critical role of vitamin B6 in plant development and stress tolerance and suggests that vitamin B6 may represent a new class of antioxidant in plants. ..
  22. Sheppard K, Soll D. On the evolution of the tRNA-dependent amidotransferases, GatCAB and GatDE. J Mol Biol. 2008;377:831-44 pubmed publisher
    ..Archaeal GatCAB, on the other hand, has not favored a distinct tRNA(Asn), suggesting that tRNA(Asn) recognition is not a major barrier to the retention of asparaginyl-tRNA synthetase in many Archaea. ..
  23. Leuendorf J, Genau A, Szewczyk A, Mooney S, Drewke C, Leistner E, et al. The Pdx1 family is structurally and functionally conserved between Arabidopsis thaliana and Ginkgo biloba. FEBS J. 2008;275:960-9 pubmed publisher
    ..Overall, this study provides a first description of Ginkgo vitamin B6 metabolism, and demonstrates a high degree of conservation between Ginkgo and Arabidopsis. ..
  24. Ferreira Junior J, Bleicher L, Barros M. Her2p molecular modeling, mutant analysis and intramitochondrial localization. Fungal Genet Biol. 2013;60:133-9 pubmed publisher
    ..For instance, her2/ts11 mutant showed its fermentative growth impaired, and poorly rescued by GTF1 indicating that Her2p unknown function in the mitochondria outer membrane affects cell viability. ..
  25. Maillard A, Biarrotte Sorin S, Villet R, Mesnage S, Bouhss A, Sougakoff W, et al. Structure-based site-directed mutagenesis of the UDP-MurNAc-pentapeptide-binding cavity of the FemX alanyl transferase from Weissella viridescens. J Bacteriol. 2005;187:3833-8 pubmed
  26. Nagao A, Suzuki T, Katoh T, Sakaguchi Y, Suzuki T. Biogenesis of glutaminyl-mt tRNAGln in human mitochondria. Proc Natl Acad Sci U S A. 2009;106:16209-14 pubmed publisher
  27. González E, Danehower D, Daub M. Vitamer levels, stress response, enzyme activity, and gene regulation of Arabidopsis lines mutant in the pyridoxine/pyridoxamine 5'-phosphate oxidase (PDX3) and the pyridoxal kinase (SOS4) genes involved in the vitamin B6 salvage pathway. Plant Physiol. 2007;145:985-96 pubmed
    ..Increased expression of salvage and some of the de novo pathway genes was observed in both the pdx3 and sos4 mutants. In all mutants, increased expression was more dramatic for the salvage pathway genes. ..
  28. Huot J, Balg C, Jahn D, Moser J, Emond A, Blais S, et al. Mechanism of a GatCAB amidotransferase: aspartyl-tRNA synthetase increases its affinity for Asp-tRNA(Asn) and novel aminoacyl-tRNA analogues are competitive inhibitors. Biochemistry. 2007;46:13190-8 pubmed
  29. Bailly M, Blaise M, Lorber B, Becker H, Kern D. The transamidosome: a dynamic ribonucleoprotein particle dedicated to prokaryotic tRNA-dependent asparagine biosynthesis. Mol Cell. 2007;28:228-39 pubmed
    ..We propose that formation of a ribonucleoprotein is a general feature for tRNA-dependent amino acid biosynthetic pathways that are remnants of earlier stages when amino acid synthesis and tRNA aminoacylation were coupled. ..
  30. Tumbula D, Becker H, Chang W, Soll D. Domain-specific recruitment of amide amino acids for protein synthesis. Nature. 2000;407:106-10 pubmed
    ..Closer inspection of the two amidotransferases reveals that each of them recruited a metabolic enzyme to aid its function; this provides direct evidence for a relationship between amino-acid metabolism and protein biosynthesis. ..
  31. Titiz O, Tambasco Studart M, Warzych E, Apel K, Amrhein N, Laloi C, et al. PDX1 is essential for vitamin B6 biosynthesis, development and stress tolerance in Arabidopsis. Plant J. 2006;48:933-46 pubmed
    ..Furthermore, we provide evidence that in addition to being essential for plant growth and development, vitamin B6 also plays a role in stress tolerance and photoprotection of plants. ..
  32. Frechin M, Duchene A, Becker H. Translating organellar glutamine codons: a case by case scenario?. RNA Biol. 2009;6:31-4 pubmed
    ..Indeed, QRS activity was found in protozoan mitochondria while AdT activity was characterized in plant organelles. The pathway for Q-tRNA(Q) synthesis in yeast and mammals mitochondria is still questionable. ..
  33. Horiuchi K, Harpel M, Shen L, Luo Y, Rogers K, Copeland R. Mechanistic studies of reaction coupling in Glu-tRNAGln amidotransferase. Biochemistry. 2001;40:6450-7 pubmed
  34. Deniziak M, Sauter C, Becker H, Giege R, Kern D. Crystallization and preliminary X-ray characterization of the atypical glutaminyl-tRNA synthetase from Deinococcus radiodurans. Acta Crystallogr D Biol Crystallogr. 2004;60:2361-3 pubmed
    ..Orthorhombic crystals were obtained that belong to space group P2(1)2(1)2(1) and diffract to 2.3 A resolution. The crystal structure was solved by molecular replacement using the structure of E. coli GlnRS as a search model. ..
  35. Cathopoulis T, Chuawong P, Hendrickson T. A thin-layer electrophoretic assay for Asp-tRNAAsn/Glu-tRNAGln amidotransferase. Anal Biochem. 2007;360:151-3 pubmed
  36. Sheppard K, Akochy P, Salazar J, Soll D. The Helicobacter pylori amidotransferase GatCAB is equally efficient in glutamine-dependent transamidation of Asp-tRNAAsn and Glu-tRNAGln. J Biol Chem. 2007;282:11866-73 pubmed
    ..Therefore, bacterial amide aminoacyl-tRNA formation is intimately tied to amide amino acid metabolism. ..
  37. Bailly M, Giannouli S, Blaise M, Stathopoulos C, Kern D, Becker H. A single tRNA base pair mediates bacterial tRNA-dependent biosynthesis of asparagine. Nucleic Acids Res. 2006;34:6083-94 pubmed
    ..In the light of these results we propose that bacterial and archaeal AdTs use kingdom-specific signals to catalyze the tRNA-dependent formations of Asn and Gln. ..
  38. Tran P, Nichols B. Expression of Escherichia coli pabA. J Bacteriol. 1991;173:3680-7 pubmed
    ..Disruption of the secondary structure by mutation allowed expression of pabA from P2, as did translation of ribosomes into the fic-pabA intergenic region. ..
  39. Raschke M, Boycheva S, Crèvecoeur M, Nunes Nesi A, Witt S, Fernie A, et al. Enhanced levels of vitamin B(6) increase aerial organ size and positively affect stress tolerance in Arabidopsis. Plant J. 2011;66:414-32 pubmed publisher
    ..In particular, the plants show an increased resistance to paraquat and photoinhibition, and they attenuate the cell death response observed in the conditional flu mutant. ..
  40. Belke D. Swim-exercised mice show a decreased level of protein O-GlcNAcylation and expression of O-GlcNAc transferase in heart. J Appl Physiol (1985). 2011;111:157-62 pubmed publisher
  41. Walker M, DeMoss J. Deletion analysis of domain independence in the TRP1 gene product of Neurospora crassa. Mol Gen Genet. 1990;223:49-57 pubmed
  42. Fishman B, Segev H, Kopper O, Nissenbaum J, Schulman M, Benvenisty N, et al. Targeting pancreatic progenitor cells in human embryonic stem cell differentiation for the identification of novel cell surface markers. Stem Cell Rev. 2012;8:792-802 pubmed publisher
    ..These findings may help in optimizing conditions for ultimately generating and isolating beta cells for transplantation therapy. ..
  43. Hu Y, Riesland L, Paterson A, Kudlow J. Phosphorylation of mouse glutamine-fructose-6-phosphate amidotransferase 2 (GFAT2) by cAMP-dependent protein kinase increases the enzyme activity. J Biol Chem. 2004;279:29988-93 pubmed
    ..GFAT2 is, therefore, an isoenzyme of GFAT1, but its regulation by cAMP is the opposite, allowing differential regulation of the hexosamine pathway in specialized tissues. ..
  44. Fan Y, Newman T, Linardopoulou E, Trask B. Gene content and function of the ancestral chromosome fusion site in human chromosome 2q13-2q14.1 and paralogous regions. Genome Res. 2002;12:1663-72 pubmed
    ..This study illustrates that the duplication and rearrangement of subtelomeric and pericentromeric regions have functional relevance to human biology; these processes can change gene dosage and/or generate genes with new functions. ..
  45. Maggio Hall L, Escalante Semerena J. In vitro synthesis of the nucleotide loop of cobalamin by Salmonella typhimurium enzymes. Proc Natl Acad Sci U S A. 1999;96:11798-803 pubmed
  46. Avila C, M rquez A, Pajuelo P, Cannell M, Wallsgrove R, Forde B. Cloning and sequence analysis of a cDNA for barley ferredoxin-dependent glutamate synthase and molecular analysis of photorespiratory mutants deficient in the enzyme. Planta. 1993;189:475-83 pubmed
    ..7 kb, the other smaller. Using a set of wheat-barley telosomic addition lines we have assigned the Fd-GOGAT structural locus to the short arm of chromosome 2...
  47. Morris J, Bergman L, Kruyer A, Gertsberg M, Guigova A, Arias R, et al. Mutations in the Drosophila mitochondrial tRNA amidotransferase, bene/gatA, cause growth defects in mitotic and endoreplicating tissues. Genetics. 2008;178:979-87 pubmed publisher
    ..gatA mutant eye clones exhibit growth and differentiation defects, indicating that gatA expression is required cell autonomously for normal growth. The gatA gene is widely expressed in mitotic and endoreplicating tissues. ..
  48. Bauby H, Saint Girons I, Picardeau M. Construction and complementation of the first auxotrophic mutant in the spirochaete Leptospira meyeri. Microbiology. 2003;149:689-93 pubmed
    ..The authors have also characterized a second selectable marker that allows the construction of a spectinomycin-resistant L. meyeri-E. coli shuttle vector and the functional complementation of the L. meyeri trpE mutant. ..
  49. Kwak J, Shin K, Woo J, Kim M, Kim S, Eom S, et al. Expression, purification, and crystallization of glutamyl-tRNA(Gln) specific amidotransferase from Bacillus stearothermophilus. Mol Cells. 2002;14:374-81 pubmed
    ..Although Glu-AdTases from both B. subtilis and B. stearothermophilus were subjected to crystallization, the micro-crystals were only obtained from the B. stearothermophilus enzyme. ..
  50. Chittur S, Klem T, Shafer C, Davisson V. Mechanism for acivicin inactivation of triad glutamine amidotransferases. Biochemistry. 2001;40:876-87 pubmed
    ..Stabilization of the imine-thioether intermediate by the oxyanion hole in triad glutamine amidotransferases appears to confer the high degree of specificity for acivicin inhibition and relates to a common mechanism for inactivation...
  51. Mantsala P, Zalkin H. Glutamine amidotransferase function. Replacement of the active-site cysteine in glutamine phosphoribosylpyrophosphate amidotransferase by site-directed mutagenesis. J Biol Chem. 1984;259:14230-6 pubmed
    ..Alternative enzymatic and autocatalytic processing mechanisms were considered. The available evidence favors autocatalytic NH2-terminal undecapeptide processing. ..
  52. Mellal D, Fonvielle M, Santarem M, Chemama M, Schneider Y, Iannazzo L, et al. Synthesis and biological evaluation of non-isomerizable analogues of Ala-tRNA(Ala). Org Biomol Chem. 2013;11:6161-9 pubmed publisher
    ..The non-isomerizable 2' and 3' regioisomers were not used as substrates by FemX(Wv), an alanyl-transferase essential for peptidoglycan synthesis, but inhibited this enzyme with IC50 of 5.8 and 5.5 ?M, respectively. ..
  53. Bazurto J, Farley K, Downs D. An Unexpected Route to an Essential Cofactor: Escherichia coli Relies on Threonine for Thiamine Biosynthesis. MBio. 2016;7:e01840-15 pubmed publisher
    ..These data show that two closely related organisms can have distinct metabolic network structures despite having similar enzyme components, thus emphasizing caveats associated with predicting metabolic potential from genome content. ..