carbon nitrogen ligases with glutamine as amide n donor


Summary: Enzymes that catalyze the joining of glutamine-derived ammonia and another molecule. The linkage is in the form of a carbon-nitrogen bond. EC 6.3.5.

Top Publications

  1. Anand R, Hoskins A, Bennett E, Sintchak M, Stubbe J, Ealick S. A model for the Bacillus subtilis formylglycinamide ribonucleotide amidotransferase multiprotein complex. Biochemistry. 2004;43:10343-52 pubmed
    ..Both models place key conserved residues at the ATP/FGAR binding site and at a structural ADP binding site. The homology model is consistent with biochemical studies on the reconstituted complex. ..
  2. Batra R, Christendat D, Edwards A, Arrowsmith C, Tong L. Crystal structure of MTH169, a crucial component of phosphoribosylformylglycinamidine synthetase. Proteins. 2002;49:285-8 pubmed publisher
  3. Morar M, Anand R, Hoskins A, Stubbe J, Ealick S. Complexed structures of formylglycinamide ribonucleotide amidotransferase from Thermotoga maritima describe a novel ATP binding protein superfamily. Biochemistry. 2006;45:14880-95 pubmed
  4. Anand R, Hoskins A, Stubbe J, Ealick S. Domain organization of Salmonella typhimurium formylglycinamide ribonucleotide amidotransferase revealed by X-ray crystallography. Biochemistry. 2004;43:10328-42 pubmed
    ..The N-terminal (PurS-like) domain is hypothesized to form the putative channel through which ammonia passes from the glutaminase domain to the FGAM synthetase domain. ..
  5. Yoshida K, Fujita Y, Ehrlich S. Three asparagine synthetase genes of Bacillus subtilis. J Bacteriol. 1999;181:6081-91 pubmed
    ..subtilis might have yet another asparagine synthetase, not recognized by sequence analysis. The strains lacking asnO failed to sporulate, indicating an involvement of this gene in sporulation. ..
  6. Raushel F, Thoden J, Holden H. The amidotransferase family of enzymes: molecular machines for the production and delivery of ammonia. Biochemistry. 1999;38:7891-9 pubmed
    ..Molecular tunnels between distant active sites have also been identified in tryptophan synthase and glutamine phosphoribosyl pyrophosphate amidotransferase and are likely architectural features in an expanding list of enzymes. ..
  7. Cantoni R, Branzoni M, Labò M, Rizzi M, Riccardi G. The MTCY428.08 gene of Mycobacterium tuberculosis codes for NAD+ synthetase. J Bacteriol. 1998;180:3218-21 pubmed
    ..Our results demonstrate that the MTCY428.08 gene of M. tuberculosis is the structural gene for NAD+ synthetase. ..
  8. Mathews I, Krishna S, Schwarzenbacher R, McMullan D, Jaroszewski L, Miller M, et al. Crystal structure of phosphoribosylformyl-glycinamidine synthase II, PurS subunit (TM1244) from Thermotoga maritima at 1.90 A resolution. Proteins. 2006;65:249-54 pubmed
  9. Hoskins A, Anand R, Ealick S, Stubbe J. The formylglycinamide ribonucleotide amidotransferase complex from Bacillus subtilis: metabolite-mediated complex formation. Biochemistry. 2004;43:10314-27 pubmed
    ..The implications of these observations are discussed with respect to ammonia channeling. ..

More Information


  1. Mathews I, Krishna S, Schwarzenbacher R, McMullan D, Abdubek P, Ambing E, et al. Crystal structure of phosphoribosylformylglycinamidine synthase II (smPurL) from Thermotoga maritima at 2.15 A resolution. Proteins. 2006;63:1106-11 pubmed
  2. Schendel F, Mueller E, Stubbe J, Shiau A, Smith J. Formylglycinamide ribonucleotide synthetase from Escherichia coli: cloning, sequencing, overproduction, isolation, and characterization. Biochemistry. 1989;28:2459-71 pubmed
    ..Incubation of [18O]FGAR with enzyme, ATP, and glutamine results in quantitative transfer of the 18O to Pi. ..
  3. Maruoka S, Horita S, Lee W, Nagata K, Tanokura M. Crystal structure of the ATPPase subunit and its substrate-dependent association with the GATase subunit: a novel regulatory mechanism for a two-subunit-type GMP synthetase from Pyrococcus horikoshii OT3. J Mol Biol. 2010;395:417-29 pubmed publisher
    ..horikoshii OT3) alone is inactive, and that all substrates of PH-ATPPase except for ammonia (Mg(2+), ATP and XMP) are required to stabilize the active complex of PH-ATPPase and PH-GATase subunits. ..
  4. Nagy P, McCorkle G, Zalkin H. purU, a source of formate for purT-dependent phosphoribosyl-N-formylglycinamide synthesis. J Bacteriol. 1993;175:7066-73 pubmed
    ..On the basis of the growth of purU, purN, and purU purN mutants, it appears that PurU provides the major source of formate for the purT-dependent synthesis of FGAR...
  5. Berges H, Checroun C, Guiral S, Garnerone A, Boistard P, Batut J. A glutamine-amidotransferase-like protein modulates FixT anti-kinase activity in Sinorhizobium meliloti. BMC Microbiol. 2001;1:6 pubmed
    ..A proposed role for asnO might be to couple nitrogen fixation gene expression in S. meliloti to the nitrogen needs of the cells. ..
  6. Thoden J, Huang X, Raushel F, Holden H. Carbamoyl-phosphate synthetase. Creation of an escape route for ammonia. J Biol Chem. 2002;277:39722-7 pubmed
    ..The substitution also effected the disposition of several key catalytic amino acid side chains in the small subunit active site. ..
  7. Yang H, Park S, Nolan W, Lu C, Abdelal A. Cloning and characterization of the arginine-specific carbamoyl-phosphate synthetase from Bacillus stearothermophilus. Eur J Biochem. 1997;249:443-9 pubmed
    ..These results indicate that cellular factors, probably chaperonins, are necessary for thermal stability of proteins at and below the optimal temperature for this thermophile. ..
  8. Fang P, Wang Z, Sachs M. Evolutionarily conserved features of the arginine attenuator peptide provide the necessary requirements for its function in translational regulation. J Biol Chem. 2000;275:26710-9 pubmed
    ..These data indicate that the highly evolutionarily conserved peptide core functions within the ribosome to cause stalling; translational events at a potential stall site can influence the extent of stalling there. ..
  9. 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...
  10. Li C, Kappock T, Stubbe J, Weaver T, Ealick S. X-ray crystal structure of aminoimidazole ribonucleotide synthetase (PurM), from the Escherichia coli purine biosynthetic pathway at 2.5 A resolution. Structure. 1999;7:1155-66 pubmed
    ..Sequence searches suggest that two successive enzymes in the purine biosynthetic pathway, proposed to use similar chemistries, will have similar ATP-binding domains. ..
  11. Poggio S, Domeinzain C, Osorio A, Camarena L. The nitrogen assimilation control (Nac) protein represses asnC and asnA transcription in Escherichia coli. FEMS Microbiol Lett. 2002;206:151-6 pubmed
    ..These results allow us to conclude that asnA transcription is regulated by two different mechanisms that respond to different effectors: nitrogen and asparagine availability. ..
  12. Lu C, Houghton J, Abdelal A. Characterization of the arginine repressor from Salmonella typhimurium and its interactions with the carAB operator. J Mol Biol. 1992;225:11-24 pubmed
    ..T-rich regions rather than on the specific nucleotide sequence. ..
  13. Wang Z, Gaba A, Sachs M. A highly conserved mechanism of regulated ribosome stalling mediated by fungal arginine attenuator peptides that appears independent of the charging status of arginyl-tRNAs. J Biol Chem. 1999;274:37565-74 pubmed
    ..Therefore, AAP-mediated Arg-specific regulation appeared independent of the charging status of arginyl-tRNA. ..
  14. Pearson D, Dawling S, Walsh W, Haines J, Christman B, Bazyk A, et al. Neonatal pulmonary hypertension--urea-cycle intermediates, nitric oxide production, and carbamoyl-phosphate synthetase function. N Engl J Med. 2001;344:1832-8 pubmed
  15. Gong X, Fu Y, Jiang D, Li G, Yi X, Peng Y. L-arginine is essential for conidiation in the filamentous fungus Coniothyrium minitans. Fungal Genet Biol. 2007;44:1368-79 pubmed
    ..This work presents the first report that L-arginine is involved in conidiation of C. minitans, and the possibility of L-arginine-derived nitric oxide-mediated conidiation among fungi and possible modes of action are discussed. ..
  16. An S, Kumar R, Sheets E, Benkovic S. Reversible compartmentalization of de novo purine biosynthetic complexes in living cells. Science. 2008;320:103-6 pubmed publisher
    ..Collectively, the data provide strong evidence for the formation of a multi-enzyme complex, the "purinosome," to carry out de novo purine biosynthesis in cells. ..
  17. Min B, Pelaschier J, Graham D, Tumbula Hansen D, Soll D. Transfer RNA-dependent amino acid biosynthesis: an essential route to asparagine formation. Proc Natl Acad Sci U S A. 2002;99:2678-83 pubmed
  18. Yamagata H, Nakajima A, Bowler C, Iwasaki T. Molecular cloning and characterization of a cDNA encoding asparagine synthetase from soybean (Glycine max L.) cell cultures. Biosci Biotechnol Biochem. 1998;62:148-50 pubmed
  19. Henikoff S, Keene M, Sloan J, Bleskan J, Hards R, Patterson D. Multiple purine pathway enzyme activities are encoded at a single genetic locus in Drosophila. Proc Natl Acad Sci U S A. 1986;83:720-4 pubmed
    ..A smaller protein appears to possess only GARS activity. Therefore, alternative mRNA processing can allow cells to produce enzyme activities in forms that are either linked or unlinked to other activities. ..
  20. Sampei G, Mizobuchi K. The organization of the purL gene encoding 5'-phosphoribosylformylglycinamide amidotransferase of Escherichia coli. J Biol Chem. 1989;264:21230-8 pubmed
    ..coli purL gene is a fused gene of at least three different gene families. The highly repetitive sequences of the E. coli genome appeared to play an important role in the process of the gene fusion. ..
  21. Vosatka R. Persistent pulmonary hypertension of the newborn. N Engl J Med. 2002;346:864 pubmed
  22. Fang P, Spevak C, Wu C, Sachs M. A nascent polypeptide domain that can regulate translation elongation. Proc Natl Acad Sci U S A. 2004;101:4059-64 pubmed
    ..These data provide precedents for translational strategies that would allow domains within nascent polypeptide chains to modulate gene expression. ..
  23. Giani S, Manoni M, Breviario D. Cloning and transcriptional analysis of the ADE6 gene of Saccharomyces cerevisiae. Gene. 1991;107:149-54 pubmed
    ..Disappearance of the larger, but not the smaller, transcript is associated with ade6 mutations. A threefold repression in the amount of the 5-kb ADE6 mRNA is observed when growth medium is supplemented with exogenous adenine. ..
  24. Alonso E, Rubio V. Affinity cleavage of carbamoyl-phosphate synthetase I localizes regions of the enzyme interacting with the molecule of ATP that phosphorylates carbamate. Eur J Biochem. 1995;229:377-84 pubmed
  25. Gu Z, Martindale D, Lee B. Isolation and complete sequence of the purL gene encoding FGAM synthase II in Lactobacillus casei. Gene. 1992;119:123-6 pubmed
    ..All these genes are organized in an operon similar to that of B. subtilis. In contrast, the corresponding genes from E. coli and Salmonella typhimurium are scattered through the genome. ..
  26. Patterson D, Bleskan J, Gardiner K, Bowersox J. Human phosphoribosylformylglycineamide amidotransferase (FGARAT): regional mapping, complete coding sequence, isolation of a functional genomic clone, and DNA sequence analysis. Gene. 1999;239:381-91 pubmed
    ..The isolation of this gene means that DNA clones for all the 10 steps of IMP synthesis have been isolated from humans or other mammals. ..
  27. Tiong S, Keizer C, Nash D, Bleskan J, Patterson D. Drosophila purine auxotrophy: new alleles of adenosine 2 exhibiting a complex visible phenotype. Biochem Genet. 1989;27:333-48 pubmed
    ..Cytogenetic analysis places the locus in the interband proximal to 26B1-2. ..
  28. Luo Z, Freitag M, Sachs M. Translational regulation in response to changes in amino acid availability in Neurospora crassa. Mol Cell Biol. 1995;15:5235-45 pubmed
    ..We examined the regulation of arg-2-lacZ reporter genes containing or lacking the uORF start codon; the capacity for arg-2 uORF translation appeared critical for controlling gene expression. ..
  29. Saxild H, Nygaard P. The yexA gene product is required for phosphoribosylformylglycinamidine synthetase activity in Bacillus subtilis. Microbiology. 2000;146 ( Pt 4):807-14 pubmed publisher
    ..The designation purS is proposed for this novel function in purine biosynthesis in B. subtilis...
  30. Hood H, Spevak C, Sachs M. Evolutionary changes in the fungal carbamoyl-phosphate synthetase small subunit gene and its associated upstream open reading frame. Fungal Genet Biol. 2007;44:93-104 pubmed
    ..A diverged Basidiomycete AAP was shown to retain function as an Arg-specific negative regulator of translation. ..
  31. Orbach M, Sachs M, Yanofsky C. The Neurospora crassa arg-2 locus. Structure and expression of the gene encoding the small subunit of arginine-specific carbamoyl phosphate synthetase. J Biol Chem. 1990;265:10981-7 pubmed
    ..Four copies of the sequence TGACTC, the binding site for the CPC1 regulatory protein, are found in the arg-2 genetic region. Two copies are located upstream of the mRNA start sites, and two are present within introns in the arg-2 uORF. ..
  32. Davids W, Gamieldien J, Liberles D, Hide W. Positive selection scanning reveals decoupling of enzymatic activities of carbamoyl phosphate synthetase in Helicobacter pylori. J Mol Evol. 2002;54:458-64 pubmed
    ..Implications of these findings for a metabolic enzyme under positive selection are discussed in terms of the mechanisms of H. pylori pathogenesis. ..
  33. Maegawa T, Karasawa T, Ohta T, Wang X, Kato H, Hayashi H, et al. Linkage between toxin production and purine biosynthesis in Clostridium difficile. J Med Microbiol. 2002;51:34-41 pubmed
    ..These results suggest that accumulation of formylglycinamide ribonucleotide (FGAR), a substrate of FGAM synthetase, enhances toxin production by C difficile and depletion of FGAR reduces toxin production. ..
  34. Vaishnav P, Randev S, Jatiani S, Aggarwal S, Keharia H, Vyas P, et al. Characterization of carbamoyl phosphate synthetase of Streptomyces spp. Indian J Exp Biol. 2000;38:931-5 pubmed
  35. Boritzki T, Jackson R, Morris H, Weber G. Guanosine-5'-phosphate synthetase and guanosine-5'-phosphate kinase in rat hepatomas and kidney tumors. Biochim Biophys Acta. 1981;658:102-10 pubmed
    ..These results indicate that GMP synthetase activity was linked with cellular proliferation in differentiating, regenerating and neoplastic tissues. ..
  36. Penverne B, Belkaid M, Herve G. In situ behavior of the pyrimidine pathway enzymes in Saccharomyces cerevisiae. 4. The channeling of carbamylphosphate to aspartate transcarbamylase and its partition in the pyrimidine and arginine pathways. Arch Biochem Biophys. 1994;309:85-93 pubmed
    ..The use of a mutant form of the complex suggests that it is between the carbamylphosphate synthetase and aspartate transcarbamylase catalytic sites belonging to the same polypeptide chain that channeling occurs. ..
  37. Morita Y, Sakai T, Araki S, Araki T, Masuyama Y. Nicotinamide adenine dinucleotide synthetase activity in erythrocytes as a tool for the biological monitoring of lead exposure. Int Arch Occup Environ Health. 1997;70:195-8 pubmed
    ..4 mumol/h per gHb, which were higher than those of ALAD activity. These results show an apparent dose-effect relationship of NADS activity versus Pb-B. NADS activity can be used for the biological monitoring of lead exposure. ..
  38. Wang Z, Sachs M. Ribosome stalling is responsible for arginine-specific translational attenuation in Neurospora crassa. Mol Cell Biol. 1997;17:4904-13 pubmed
    ..These data suggest that arginine increases ribosomal stalling and thereby decreases translation from the downstream initiation codon. ..
  39. Andreichuk YuV -, Domkin V, Ryzhova T, Koulikov V, Kostikova T. ADE6 gene of Saccharomyces cerevisiae yeast encoding formylglycinamidine-ribonucleotide synthetase. Cloning, sequencing, and analysis. Biochemistry (Mosc). 1997;62:742-52 pubmed
    ..Repeats of similar patterns of conserved amino acids were also detected in the structure of all other FGAM-synthetases. A homology of FGAM-synthetases with certain proteins of viruses from the Herpesviridae family was found. ..
  40. Tesson A, Soper T, Ciustea M, Richards N. Revisiting the steady state kinetic mechanism of glutamine-dependent asparagine synthetase from Escherichia coli. Arch Biochem Biophys. 2003;413:23-31 pubmed
    ..The coupling of glutaminase and synthetase activities in AS is therefore different from that observed in all other well-characterized glutamine-dependent amidotransferases. ..
  41. Vaghchhipawala Z, Schlueter J, Shoemaker R, Mackenzie S. Soybean FGAM synthase promoters direct ectopic nematode feeding site activity. Genome. 2004;47:404-13 pubmed
    ..Although a nematode-responsive element could not be identified, the observed expression of GFP within feeding sites supports the hypothesis that plant gene expression is redirected within feeding sites to benefit the parasite. ..
  42. Bhushan S, Meyer H, Starosta A, Becker T, Mielke T, Berninghausen O, et al. Structural basis for translational stalling by human cytomegalovirus and fungal arginine attenuator peptide. Mol Cell. 2010;40:138-46 pubmed publisher
    ..Our findings provide direct structural insight into two distinct eukaryotic stalling processes. ..
  43. An S, Deng Y, Tomsho J, Kyoung M, Benkovic S. Microtubule-assisted mechanism for functional metabolic macromolecular complex formation. Proc Natl Acad Sci U S A. 2010;107:12872-6 pubmed publisher
    ..Collectively, we propose a microtubule-assisted mechanism for functional purinosome formation in HeLa cells. ..
  44. Xie B, Chen D, Zhou K, Xie Y, Li Y, Hu G, et al. Symbiotic abilities of Sinorhizobium fredii with modified expression of purL. Appl Microbiol Biotechnol. 2006;71:505-14 pubmed
    ..fredii on G. max without the exogenous supplementation of any adenine or purine precursor; at least a minimal level of expression of purL is essential for effective symbiosis with soybean...
  45. Crabeel M, De Rijcke M, Seneca S, Heimberg H, Pfeiffer I, Matisova A. Further definition of the sequence and position requirements of the arginine control element that mediates repression and induction by arginine in Saccharomyces cerevisiae. Yeast. 1995;11:1367-80 pubmed
    ..The new data suggest that the arginine repressor might inhibit transcription in an active process. ..
  46. Houlberg U, Hove Jensen B, Jochimsen B, Nygaard P. Identification of the enzymatic reactions encoded by the purG and purI genes of Escherichia coli. J Bacteriol. 1983;154:1485-8 pubmed
    ..typhimurium. The gene products currently listed for the loci in E. coli are incorrect. The E. coli purG locus is equivalent to the S. typhimurium purI locus, and the E. coli purI locus is equivalent to the S. typhimurium purG locus. ..
  47. Green M, Karp P. A Bayesian method for identifying missing enzymes in predicted metabolic pathway databases. BMC Bioinformatics. 2004;5:76 pubmed
    ..Our pathway hole filler can be used not only to increase the utility of Pathway/Genome databases to both experimental and computational researchers, but also to improve predictions of protein function. ..
  48. Deras M, Chittur S, Davisson V. N2-hydroxyguanosine 5'-monophosphate is a time-dependent inhibitor of Escherichia coli guanosine monophosphate synthetase. Biochemistry. 1999;38:303-10 pubmed
    ..In addition, these results complement recent structural studies of GMPS and implicate the formation of the XMP-adenylate intermediate inducing a probable conformational change that stimulates the hydrolysis of glutamine. ..
  49. Lim A, Powers Lee S. Critical roles for arginine 1061/1060 and tyrosine 1057 in Saccharomyces cerevisiae arginine-specific carbamoyl-phosphate synthetase. Arch Biochem Biophys. 1997;339:344-52 pubmed
    ..However, tyrosine 1057 was critical for CPSase structure and the presence of one of the tandem arginyl residues at positions 1061 and 1060 was critical for CPSase catalytic function. ..
  50. Jackson M, Berthet F, Otal I, Rauzier J, Martin C, Gicquel B, et al. The Mycobacterium tuberculosis purine biosynthetic pathway: isolation and characterization of the purC and purL genes. Microbiology. 1996;142 ( Pt 9):2439-47 pubmed
    ..Transcriptional start sites were mapped for both genes, which revealed similar-10 boxes but with a higher GC content than the Escherichia coli sigma 70 consensus. ..
  51. Caperelli C, Liu D. Carbocyclic substrates for de novo purine biosynthesis. Enantiospecific synthesis and enantiospecificity of enzymatic utilization. J Biol Chem. 1992;267:9783-7 pubmed
    ..A comparison of the enzymatic processing of the (-)-enantiomers with those of the racemates indicates that in some cases, the (+)-enantiomer acts to inhibit the enzymatic activity. ..
  52. Freitag M, Dighde N, Sachs M. A UV-induced mutation in neurospora that affects translational regulation in response to arginine. Genetics. 1996;142:117-27 pubmed
    ..Comparisons with other uORF5 suggest common elements in translational control mechanisms. ..
  53. Barnes T, Bleskan J, Hart I, Walton K, Barton J, Patterson D. Purification of, generation of monoclonal antibodies to, and mapping of phosphoribosyl N-formylglycinamide amidotransferase. Biochemistry. 1994;33:1850-60 pubmed
    ..Analysis of these lines, together with two independently generated human/mouse hybrid cell lines, by both cytogenetics and immunoblotting with antibody DD2 revealed that the human FGAR amidotransferase gene is located on chromosome 17p. ..