guanosine tetraphosphate


Summary: Guanosine 5'-diphosphate 2'(3')-diphosphate. A guanine nucleotide containing four phosphate groups. Two phosphate groups are esterified to the sugar moiety in the 5' position and the other two in the 2' or 3' position. This nucleotide serves as a messenger to turn off the synthesis of ribosomal RNA when amino acids are not available for protein synthesis. Synonym: magic spot I.

Top Publications

  1. Magnusson L, Farewell A, Nystrom T. ppGpp: a global regulator in Escherichia coli. Trends Microbiol. 2005;13:236-42 pubmed
    ..In addition, new insights into the mechanism by which ppGpp affects gene expression have been achieved owing to in vitro studies of ppGpp function, complemented by structural studies of the ppGpp-RNA polymerase complex. ..
  2. Kanjee U, Ogata K, Houry W. Direct binding targets of the stringent response alarmone (p)ppGpp. Mol Microbiol. 2012;85:1029-43 pubmed publisher
    ..While the inhibition of some PLP-dependent decarboxylases by ppGpp suggests the existence of cross-talk between the acid stress and stringent response systems. ..
  3. Krásný L, Gourse R. An alternative strategy for bacterial ribosome synthesis: Bacillus subtilis rRNA transcription regulation. EMBO J. 2004;23:4473-83 pubmed
    ..subtilis RNA polymerase directly. Rather, increases in the ppGpp concentration might reduce the available GTP pools, thereby modulating rRNA promoter activity indirectly. ..
  4. Wells D, Long S. The Sinorhizobium meliloti stringent response affects multiple aspects of symbiosis. Mol Microbiol. 2002;43:1115-27 pubmed
  5. Vassylyev D, Svetlov V, Vassylyeva M, Perederina A, Igarashi N, Matsugaki N, et al. Structural basis for transcription inhibition by tagetitoxin. Nat Struct Mol Biol. 2005;12:1086-93 pubmed publisher
    ..Remodeling of the active site by metal ions could be a common theme in the regulation of catalysis by nucleic acid enzymes...
  6. Paul B, Berkmen M, Gourse R. DksA potentiates direct activation of amino acid promoters by ppGpp. Proc Natl Acad Sci U S A. 2005;102:7823-8 pubmed
  7. Bernardo L, Johansson L, Solera D, Skarfstad E, Shingler V. The guanosine tetraphosphate (ppGpp) alarmone, DksA and promoter affinity for RNA polymerase in regulation of sigma-dependent transcription. Mol Microbiol. 2006;60:749-64 pubmed
    The RNA polymerase-binding protein DksA is a cofactor required for guanosine tetraphosphate (ppGpp)-responsive control of transcription from sigma70 promoters...
  8. Dalebroux Z, Swanson M. ppGpp: magic beyond RNA polymerase. Nat Rev Microbiol. 2012;10:203-12 pubmed publisher
  9. Hesketh A, Chen W, Ryding J, Chang S, Bibb M. The global role of ppGpp synthesis in morphological differentiation and antibiotic production in Streptomyces coelicolor A3(2). Genome Biol. 2007;8:R161 pubmed
    ..In S. coelicolor, ppGpp synthesis influences the expression of several genomic elements that are particularly characteristic of streptomycete biology, notably antibiotic gene clusters, conservons, and morphogenetic proteins. ..

More Information


  1. Barker M, Gaal T, Gourse R. Mechanism of regulation of transcription initiation by ppGpp. II. Models for positive control based on properties of RNAP mutants and competition for RNAP. J Mol Biol. 2001;305:689-702 pubmed
    ..Our data also place considerable constraints on models invoking hypothetical factors that might increase amino acid promoter activity in a ppGpp-dependent fashion. ..
  2. Gaal T, Gourse R. Guanosine 3'-diphosphate 5'-diphosphate is not required for growth rate-dependent control of rRNA synthesis in Escherichia coli. Proc Natl Acad Sci U S A. 1990;87:5533-7 pubmed
    ..Therefore, growth rate-dependent control and stringent control may utilize different mechanisms for regulating stable RNA synthesis. ..
  3. Lange R, Fischer D, Hengge Aronis R. Identification of transcriptional start sites and the role of ppGpp in the expression of rpoS, the structural gene for the sigma S subunit of RNA polymerase in Escherichia coli. J Bacteriol. 1995;177:4676-80 pubmed
    ..However, experiments with the 5' deletion constructs indicate that a lack of ppGpp does affect transcriptional elongation rather than initiation. ..
  4. Zhao G, Weatherspoon N, Kong W, Curtiss R, Shi Y. A dual-signal regulatory circuit activates transcription of a set of divergent operons in Salmonella typhimurium. Proc Natl Acad Sci U S A. 2008;105:20924-9 pubmed publisher
    ..We demonstrate that SlyA mediates transcriptional activation in response to guanosine tetraphosphate, ppGpp, according to the following observations: (i) in vivo transcription of SlyA-dependent genes is ..
  5. Potrykus K, Murphy H, Philippe N, Cashel M. ppGpp is the major source of growth rate control in E. coli. Environ Microbiol. 2011;13:563-575 pubmed publisher
    ..We believe these findings strongly argue in favour of ppGpp and against redundant regulation of growth rate control by other factors in Escherichia coli and other enteric bacteria. ..
  6. Vinella D, D Ari R, Jaffe A, Bouloc P. Penicillin binding protein 2 is dispensable in Escherichia coli when ppGpp synthesis is induced. EMBO J. 1992;11:1493-501 pubmed
    ..We conclude that ppGpp regulates the transcription of a gene whose product is involved in mecillinam sensitivity, possibly as part of a chain of interacting elements which coordinate ribosomal activity with that of the PBPs. ..
  7. Baracchini E, Bremer H. Stringent and growth control of rRNA synthesis in Escherichia coli are both mediated by ppGpp. J Biol Chem. 1988;263:2597-602 pubmed
    ..In this manner, the intracellular concentration of the nucleotide guanosine tetraphosphate, ppGpp, could be varied in any desired range between 0 and 1000 pmol of ppGpp per OD460 unit of culture ..
  8. Szalewska Pałasz A. Properties of Escherichia coli RNA polymerase from a strain devoid of the stringent response alarmone ppGpp. Acta Biochim Pol. 2008;55:317-23 pubmed
    The stringent response alarmone guanosine tetraphosphate (ppGpp) affects transcription from many promoters. ppGpp binds directly to the transcription enzyme of Escherichia coli, RNA polymerase...
  9. Hammer B, Swanson M. Co-ordination of legionella pneumophila virulence with entry into stationary phase by ppGpp. Mol Microbiol. 1999;33:721-31 pubmed
    ..pneumophila to escape its spent host, to survive and disperse in the environment and to re-establish a protected intracellular replication niche. ..
  10. Kasai K, Nishizawa T, Takahashi K, Hosaka T, Aoki H, Ochi K. Physiological analysis of the stringent response elicited in an extreme thermophilic bacterium, Thermus thermophilus. J Bacteriol. 2006;188:7111-22 pubmed
    b>Guanosine tetraphosphate (ppGpp) is a key mediator of stringent control, an adaptive response of bacteria to amino acid starvation, and has thus been termed a bacterial alarmone...
  11. Aberg A, Shingler V, Balsalobre C. Regulation of the fimB promoter: a case of differential regulation by ppGpp and DksA in vivo. Mol Microbiol. 2008;67:1223-41 pubmed publisher
  12. Vrentas C, Gaal T, Ross W, Ebright R, Gourse R. Response of RNA polymerase to ppGpp: requirement for the omega subunit and relief of this requirement by DksA. Genes Dev. 2005;19:2378-87 pubmed
    ..Furthermore, these results suggest that either one or both of two short segments in the beta' subunit that physically link omega to the ppGpp-binding region of the enzyme may play crucial roles in ppGpp and DksA function. ..
  13. Gottesman S, Maurizi M. Cell biology. Surviving starvation. Science. 2001;293:614-5 pubmed
  14. Toulokhonov I, Shulgina I, Hernandez V. Binding of the transcription effector ppGpp to Escherichia coli RNA polymerase is allosteric, modular, and occurs near the N terminus of the beta'-subunit. J Biol Chem. 2001;276:1220-5 pubmed
    ..We propose that the N terminus of beta' together with the C terminus of beta constitute a modular ppGpp binding site. ..
  15. Slominska M, Neubauer P, Wegrzyn G. Regulation of bacteriophage lambda development by guanosine 5'-diphosphate-3'-diphosphate. Virology. 1999;262:431-41 pubmed
    ..Here we demonstrate that the "lysis-versus-lysogenization" decision is influenced by guanosine tetraphosphate (ppGpp), a nucleotide that is synthesized in E...
  16. Potrykus K, Cashel M. (p)ppGpp: still magical?. Annu Rev Microbiol. 2008;62:35-51 pubmed publisher
    ..Many basic questions still exist. This review tries to focus on some issues that linger even for the most widely characterized bacterial strains. ..
  17. Mechold U, Cashel M, Steiner K, Gentry D, Malke H. Functional analysis of a relA/spoT gene homolog from Streptococcus equisimilis. J Bacteriol. 1996;178:1401-11 pubmed
    ..equisimilis in S. equisimilis abolish the parental (p)ppGpp accumulation response to amino acid starvation in a manner expected for relA mutants rather than spoT mutants. ..
  18. Hernandez V, Bremer H. Guanosine tetraphosphate (ppGpp) dependence of the growth rate control of rrnB P1 promoter activity in Escherichia coli. J Biol Chem. 1990;265:11605-14 pubmed
    ..We have fused the ribosomal RNA promoter P1 from the rrnB gene of Escherichia coli to lacZ and examined its guanosine tetraphosphate (ppGpp)-dependent expression at different growth rates...
  19. Taylor C, Beresford M, Epton H, Sigee D, Shama G, Andrew P, et al. Listeria monocytogenes relA and hpt mutants are impaired in surface-attached growth and virulence. J Bacteriol. 2002;184:621-8 pubmed
    ..monocytogenes in the host. Taken as a whole, this study provides new information on the role of the stringent response and the physiological adaptation of L. monocytogenes for biofilm growth and pathogenesis. ..
  20. Hardiman T, Windeisen V, Ewald J, Zibek S, Schlack P, Rebell J, et al. In vitro synthesis and characterization of guanosine 3',5'-bis(diphosphate). Anal Biochem. 2008;383:337-9 pubmed publisher
    ..13)C NMR analysis enabled the structural characterization of the synthesis product and was complemented by mass spectrometry and methods that are commonly used to identify ppGpp. ..
  21. Sze C, Bernardo L, Shingler V. Integration of global regulation of two aromatic-responsive sigma(54)-dependent systems: a common phenotype by different mechanisms. J Bacteriol. 2002;184:760-70 pubmed
    ..The mechanistic implications of how each of the host factors exerts its action are discussed. ..
  22. Thompson A, Rolfe M, Lucchini S, Schwerk P, Hinton J, Tedin K. The bacterial signal molecule, ppGpp, mediates the environmental regulation of both the invasion and intracellular virulence gene programs of Salmonella. J Biol Chem. 2006;281:30112-21 pubmed
    ..This is the first demonstration that this highly conserved regulatory system is involved in bacterial virulence gene expression on a global scale. ..
  23. Wang J, Sanders G, Grossman A. Nutritional control of elongation of DNA replication by (p)ppGpp. Cell. 2007;128:865-75 pubmed
    ..This control may be important for cells to maintain genomic integrity. ..
  24. Traxler M, Chang D, Conway T. Guanosine 3',5'-bispyrophosphate coordinates global gene expression during glucose-lactose diauxie in Escherichia coli. Proc Natl Acad Sci U S A. 2006;103:2374-9 pubmed
  25. Aviv M, Giladi H, Schreiber G, Oppenheim A, Glaser G. Expression of the genes coding for the Escherichia coli integration host factor are controlled by growth phase, rpoS, ppGpp and by autoregulation. Mol Microbiol. 1994;14:1021-31 pubmed
    ..All three sites show low binding affinity to IHF suggesting that autoregulation can take place only after sufficiently high levels of IHF accumulate in the cell. ..
  26. Magnusson L, Gummesson B, Joksimović P, Farewell A, Nystrom T. Identical, independent, and opposing roles of ppGpp and DksA in Escherichia coli. J Bacteriol. 2007;189:5193-202 pubmed
    ..In addition, ppGpp and DksA have opposing effects on adhesion. In the course of our analysis, we also discovered new features of the relaxed mutant, namely, defects in cell-cell aggregation and motility. ..
  27. Spira B, Hu X, Ferenci T. Strain variation in ppGpp concentration and RpoS levels in laboratory strains of Escherichia coli K-12. Microbiology. 2008;154:2887-95 pubmed publisher
    ..coli. ..
  28. Baracchini E, Bremer H. Control of rRNA synthesis in Escherichia coli at increased rrn gene dosage. Role of guanosine tetraphosphate and ribosome feedback. J Biol Chem. 1991;266:11753-60 pubmed
    ..the fraction of total RNA synthesis that is rRNA and tRNA (rs/rt), the cytoplasmic concentration of guanosine tetraphosphate (ppGpp), and the absolute rates of RNA and protein synthesis...
  29. Barker M, Gaal T, Josaitis C, Gourse R. Mechanism of regulation of transcription initiation by ppGpp. I. Effects of ppGpp on transcription initiation in vivo and in vitro. J Mol Biol. 2001;305:673-88 pubmed
    ..The accompanying paper evaluates potential models for positive control of amino acid promoters by ppGpp that might explain the requirement of ppGpp for amino acid prototrophy. ..
  30. Trautinger B, Jaktaji R, Rusakova E, Lloyd R. RNA polymerase modulators and DNA repair activities resolve conflicts between DNA replication and transcription. Mol Cell. 2005;19:247-58 pubmed
    ..When arrays do obstruct replication, the consequences are resolved by one of the many pathways available to rescue stalled forks. ..
  31. Sun D, Lee G, Lee J, Kim H, Rhee H, Park S, et al. A metazoan ortholog of SpoT hydrolyzes ppGpp and functions in starvation responses. Nat Struct Mol Biol. 2010;17:1188-94 pubmed publisher
    ..These data suggest that metazoan SpoT orthologs have an evolutionarily conserved function in starvation responses. ..
  32. Dalebroux Z, Yagi B, Sahr T, Buchrieser C, Swanson M. Distinct roles of ppGpp and DksA in Legionella pneumophila differentiation. Mol Microbiol. 2010;76:200-19 pubmed publisher
    ..Here we exploit the pathogen's life cycle to examine how guanosine tetraphosphate (ppGpp) and DksA cooperate to govern bacterial differentiation...
  33. Mechold U, Murphy H, Brown L, Cashel M. Intramolecular regulation of the opposing (p)ppGpp catalytic activities of Rel(Seq), the Rel/Spo enzyme from Streptococcus equisimilis. J Bacteriol. 2002;184:2878-88 pubmed
    ..coli by inhibiting unregulated degradation and restoring regulated synthetic activity. Reciprocal intramolecular regulation of the dual activities may be a general intrinsic feature of Rel/Spo homolog proteins. ..
  34. Eymann C, Homuth G, Scharf C, Hecker M. Bacillus subtilis functional genomics: global characterization of the stringent response by proteome and transcriptome analysis. J Bacteriol. 2002;184:2500-20 pubmed
    ..A passive model is preferred to explain this positive control relying on the redistribution of the RNA polymerase under the influence of (p)ppGpp. ..
  35. Gentry D, Xiao H, Burgess R, Cashel M. The omega subunit of Escherichia coli K-12 RNA polymerase is not required for stringent RNA control in vivo. J Bacteriol. 1991;173:3901-3 pubmed
    ..We conclude that omega protein is not necessary for the operation of the stringent RNA control response. ..
  36. Mouery K, Rader B, Gaynor E, Guillemin K. The stringent response is required for Helicobacter pylori survival of stationary phase, exposure to acid, and aerobic shock. J Bacteriol. 2006;188:5494-500 pubmed
    ..In addition, the spoT deletion mutant is unable to survive specific environmental stresses, including aerobic shock and acid exposure, which are likely to be encountered by this bacterium during infection and transmission. ..
  37. Laurie A, Bernardo L, Sze C, Skarfstad E, Szalewska Palasz A, Nystrom T, et al. The role of the alarmone (p)ppGpp in sigma N competition for core RNA polymerase. J Biol Chem. 2003;278:1494-503 pubmed
  38. Schneider D, Murray H, Gourse R. Measuring control of transcription initiation by changing concentrations of nucleotides and their derivatives. Methods Enzymol. 2003;370:606-17 pubmed
  39. Potrykus K, Wegrzyn G, Hernandez V. Direct stimulation of the lambdapaQ promoter by the transcription effector guanosine-3',5'-(bis)pyrophosphate in a defined in vitro system. J Biol Chem. 2004;279:19860-6 pubmed
    ..Our data indicate that the mechanism underlying ppGpp stimulation of paQ is due to an increased rate of productive open complex formation. ..
  40. Nakanishi N, Abe H, Ogura Y, Hayashi T, Tashiro K, Kuhara S, et al. ppGpp with DksA controls gene expression in the locus of enterocyte effacement (LEE) pathogenicity island of enterohaemorrhagic Escherichia coli through activation of two virulence regulatory genes. Mol Microbiol. 2006;61:194-205 pubmed publisher
    ..These findings suggest that the regulation of virulence genes in EHEC is integrated with E. coli's stringent response system, through the regulation of virulence regulatory genes...
  41. Traxler M, Zacharia V, Marquardt S, Summers S, Nguyen H, Stark S, et al. Discretely calibrated regulatory loops controlled by ppGpp partition gene induction across the 'feast to famine' gradient in Escherichia coli. Mol Microbiol. 2011;79:830-45 pubmed publisher
    ..The emergent regulatory structure insures that stress survival circuits are only triggered if homeostatic metabolic networks fail to compensate for environmental deficiencies. ..
  42. Rymer R, Solorio F, Tehranchi A, Chu C, Corn J, Keck J, et al. Binding mechanism of metal?NTP substrates and stringent-response alarmones to bacterial DnaG-type primases. Structure. 2012;20:1478-89 pubmed publisher
  43. Vercruysse M, Fauvart M, Jans A, Beullens S, Braeken K, Cloots L, et al. Stress response regulators identified through genome-wide transcriptome analysis of the (p)ppGpp-dependent response in Rhizobium etli. Genome Biol. 2011;12:R17 pubmed publisher
    ..Here, we report the first in-depth analysis of the (p)ppGpp-regulon in an ?-proteobacterium using a high-resolution tiling array to better understand the pleiotropic stress phenotype of a relA/rsh mutant...
  44. Szalewska Palasz A, Wegrzyn G, Wegrzyn A. Mechanisms of physiological regulation of RNA synthesis in bacteria: new discoveries breaking old schemes. J Appl Genet. 2007;48:281-94 pubmed
    ..ii) control of DNA replication by interactions of the starvation alarmones, guanosine pentaphosphate and guanosine tetraphosphate, (p)ppGpp, with DnaG primase, (iii) a role for the DksA protein in ppGpp-mediated regulation of ..
  45. Wells D, Gaynor E. Helicobacter pylori initiates the stringent response upon nutrient and pH downshift. J Bacteriol. 2006;188:3726-9 pubmed
    ..pylori produced abundant ppGpp and less total RNA. pH downshift also caused (p)ppGpp accumulation. Our observations indicate that nutrient deprivation and acid shock activate the stringent response in H. pylori. ..
  46. Murray K, Bremer H. Control of spoT-dependent ppGpp synthesis and degradation in Escherichia coli. J Mol Biol. 1996;259:41-57 pubmed
    ..Finally, it was found that neither relC, transcriptional regulation of spoT, nor different translation starts of spoT mRNA are directly involved in the environmental control of SpoT hydrolase and PSII activities. ..
  47. Jain V, Kumar M, Chatterji D. ppGpp: stringent response and survival. J Microbiol. 2006;44:1-10 pubmed
    ..Therefore, an understanding of the physiology of stringent conditions becomes very interesting in regulation of the growth and persistence of such invading pathogens. ..
  48. Gentry D, Hernandez V, Nguyen L, Jensen D, Cashel M. Synthesis of the stationary-phase sigma factor sigma s is positively regulated by ppGpp. J Bacteriol. 1993;175:7982-9 pubmed
    ..This finding suggests that changes in ppGpp levels function both as a signal of imminent stationary phase and as a signal of perturbations in steady-state growth. ..
  49. Roberts J. Promoter-specific control of E. coli RNA polymerase by ppGpp and a general transcription factor. Genes Dev. 2009;23:143-6 pubmed publisher
  50. Da Costa X, Artz S. Mutations that render the promoter of the histidine operon of Salmonella typhimurium insensitive to nutrient-rich medium repression and amino acid downshift. J Bacteriol. 1997;179:5211-7 pubmed
    ..More specifically, the in vivo evidence shows that the region of the his promoter that includes the -10 hexamer and discriminator sequences is the target at which ppGpp stimulates transcription. ..
  51. Chakrabarty A. Nucleoside diphosphate kinase: role in bacterial growth, virulence, cell signalling and polysaccharide synthesis. Mol Microbiol. 1998;28:875-82 pubmed
    ..Specific examples of the role of Ndk in regulating growth, NTP formation and cell surface polysaccharide synthesis in two respiratory tract pathogens, Pseudomonas aeruginosa and Mycobacterium tuberculosis, are discussed. ..
  52. Dalebroux Z, Svensson S, Gaynor E, Swanson M. ppGpp conjures bacterial virulence. Microbiol Mol Biol Rev. 2010;74:171-99 pubmed publisher
    ..Here we discuss how components of the stringent response contribute to the virulence of a wide variety of pathogenic bacteria. ..
  53. Johansson L, Solera D, Bernardo L, Moscoso J, Shingler V. sigma54-RNA polymerase controls sigma70-dependent transcription from a non-overlapping divergent promoter. Mol Microbiol. 2008;70:709-23 pubmed publisher
  54. Bernardo L, Johansson L, Skarfstad E, Shingler V. sigma54-promoter discrimination and regulation by ppGpp and DksA. J Biol Chem. 2009;284:828-38 pubmed publisher
    ..The mechanism behind this difference can be traced to reduced promoter discrimination of low affinity sigma(54)-promoters that is conferred by the strong DNA binding properties of the P. putida sigma(54)-RNA polymerase holoenzyme. ..
  55. Ooga T, Ohashi Y, Kuramitsu S, Koyama Y, Tomita M, Soga T, et al. Degradation of ppGpp by nudix pyrophosphatase modulates the transition of growth phase in the bacterium Thermus thermophilus. J Biol Chem. 2009;284:15549-56 pubmed publisher
    ..These results suggest a novel mechanism of ppGpp-mediated growth control by the functional relay between Ndx8 and SpoT activity as ppGpp scavengers. ..
  56. Schreiber G, Metzger S, Aizenman E, Roza S, Cashel M, Glaser G. Overexpression of the relA gene in Escherichia coli. J Biol Chem. 1991;266:3760-7 pubmed
  57. Igarashi K, Fujita N, Ishihama A. Promoter selectivity of Escherichia coli RNA polymerase: omega factor is responsible for the ppGpp sensitivity. Nucleic Acids Res. 1989;17:8755-65 pubmed
    ..of stringently controlled Escherichia coli genes by purified RNA polymerase holoenzyme is inhibited by guanosine tetraphosphate (ppGpp)...
  58. Pizarro Cerda J, Tedin K. The bacterial signal molecule, ppGpp, regulates Salmonella virulence gene expression. Mol Microbiol. 2004;52:1827-44 pubmed
    ..An S. typhimuriumDeltarelADeltaspoT strain deficient in guanosine tetraphosphate (ppGpp) synthesis was found to be highly attenuated in vivo and non-invasive in vitro...
  59. Sze C, Shingler V. The alarmone (p)ppGpp mediates physiological-responsive control at the sigma 54-dependent Po promoter. Mol Microbiol. 1999;31:1217-28 pubmed
    ..These data provide a direct mechanistic link between the physiological status of the cell and expression from sigma 54 promoters. ..
  60. Kvint K, Farewell A, Nystrom T. RpoS-dependent promoters require guanosine tetraphosphate for induction even in the presence of high levels of sigma(s). J Biol Chem. 2000;275:14795-8 pubmed
  61. Jishage M, Kvint K, Shingler V, Nystrom T. Regulation of sigma factor competition by the alarmone ppGpp. Genes Dev. 2002;16:1260-70 pubmed
    ..Thus, the stringent response encompasses a mechanism that alters the relative competitiveness of sigma factors in accordance with cellular demands during physiological stress. ..
  62. Gropp M, Strausz Y, Gross M, Glaser G. Regulation of Escherichia coli RelA requires oligomerization of the C-terminal domain. J Bacteriol. 2001;183:570-9 pubmed
    ..Ladant, Proc. Natl. Acad. Sci. USA 95:5752-5756, 1998) indicated that the CTD (aa 564 to 744) is involved in RelA-RelA interactions. Our findings support a model in which RelA activation is regulated by its oligomerization state. ..
  63. Dozot M, Boigegrain R, Delrue R, Hallez R, Ouahrani Bettache S, Danese I, et al. The stringent response mediator Rsh is required for Brucella melitensis and Brucella suis virulence, and for expression of the type IV secretion system virB. Cell Microbiol. 2006;8:1791-802 pubmed
  64. Ito D, Kato T, Maruta T, Tamoi M, Yoshimura K, Shigeoka S. Enzymatic and molecular characterization of Arabidopsis ppGpp pyrophosphohydrolase, AtNUDX26. Biosci Biotechnol Biochem. 2012;76:2236-41 pubmed
    ..This is the first report on the molecular properties of ppGpp pyrophosphohydrolases in plants. ..
  65. Ochi K. Metabolic initiation of differentiation and secondary metabolism by Streptomyces griseus: significance of the stringent response (ppGpp) and GTP content in relation to A factor. J Bacteriol. 1987;169:3608-16 pubmed
    ..It is also suggested that A factor may render the cell sensitive to receive and respond to the specified signal molecules, presumably ppGpp (for physiological differentiation) or GTP (for morphological differentiation). ..
  66. Svitil A, Cashel M, Zyskind J. Guanosine tetraphosphate inhibits protein synthesis in vivo. A possible protective mechanism for starvation stress in Escherichia coli. J Biol Chem. 1993;268:2307-11 pubmed
  67. Chakraburtty R, White J, Takano E, Bibb M. Cloning, characterization and disruption of a (p)ppGpp synthetase gene (relA) of Streptomyces coelicolor A3(2). Mol Microbiol. 1996;19:357-368 pubmed
    ..The relA mutation had no consistent or marked effect on actinorhodin production in either liquid- or agar-grown cultures, indicating that elevated levels of (p)ppGpp are not essential for triggering the onset of antibiotic production...
  68. Wolz C, Geiger T, Goerke C. The synthesis and function of the alarmone (p)ppGpp in firmicutes. Int J Med Microbiol. 2010;300:142-7 pubmed publisher
    ..Here we will focus on basic differences between firmicutes and proteobacteria, particularly E. coli. ..
  69. Wagner R. Regulation of ribosomal RNA synthesis in E. coli: effects of the global regulator guanosine tetraphosphate (ppGpp). J Mol Microbiol Biotechnol. 2002;4:331-40 pubmed
    ..From the existing data a mechanistic model for the action of ppGpp is suggested considering structural details of RNA polymerase obtained at high resolution. ..
  70. Erickson D, Lines J, Pesci E, Venturi V, Storey D. Pseudomonas aeruginosa relA contributes to virulence in Drosophila melanogaster. Infect Immun. 2004;72:5638-45 pubmed
    ..These results suggest that adjustment of cellular ppGpp and pppGpp levels could be an important regulatory mechanism in P. aeruginosa adaptation in pathogenic relationships. ..
  71. Chatterji D, Ojha A. Revisiting the stringent response, ppGpp and starvation signaling. Curr Opin Microbiol. 2001;4:160-5 pubmed
    ..Recently, there has been renewed interest in the stringent responses of other microbes, with a view to correlating it with sporulation, virulence and long-term persistence. ..
  72. Maciag M, Kochanowska M, Lyzeń R, Wegrzyn G, Szalewska Pałasz A. ppGpp inhibits the activity of Escherichia coli DnaG primase. Plasmid. 2010;63:61-7 pubmed publisher
    ..coli DnaG primase is directly inhibited by ppGpp and pppGpp. However, contrary to the B. subtilis primase response to the stringent control alarmones, the E, coli DnaG was inhibited more efficiently by ppGpp than by pppGpp. ..
  73. English B, Hauryliuk V, Sanamrad A, Tankov S, Dekker N, Elf J. Single-molecule investigations of the stringent response machinery in living bacterial cells. Proc Natl Acad Sci U S A. 2011;108:E365-73 pubmed publisher
  74. Potrykus K, Wegrzyn G, Hernandez V. Multiple mechanisms of transcription inhibition by ppGpp at the lambdap(R) promoter. J Biol Chem. 2002;277:43785-91 pubmed
    ..Rather we conclude that the initial catalytic step of transcript formation is affected by ppGpp, specifically formation of the first phosphodiester bond is inhibited by ppGpp at lambdap(R). ..
  75. Kuroda A, Murphy H, Cashel M, Kornberg A. Guanosine tetra- and pentaphosphate promote accumulation of inorganic polyphosphate in Escherichia coli. J Biol Chem. 1997;272:21240-3 pubmed
    High levels of guanosine tetraphosphate (ppGpp) and guanosine pentaphosphate (pppGpp), generated in response to amino acid starvation in Escherichia coli, lead to massive accumulations of inorganic polyphosphate (polyP)...
  76. Brockmann Gretza O, Kalinowski J. Global gene expression during stringent response in Corynebacterium glutamicum in presence and absence of the rel gene encoding (p)ppGpp synthase. BMC Genomics. 2006;7:230 pubmed
    ..Notable are the rel-dependent regulation of the nitrogen metabolism genes and the rel-independent regulation of the genes encoding ribosomal proteins. ..
  77. Negre D, Cortay J, Donini P, Cozzone A. Relationship between guanosine tetraphosphate and accuracy of translation in Salmonella typhimurium. Biochemistry. 1989;28:1814-9 pubmed
    ..abstract truncated at 250 words) ..
  78. Kristensen O, Ross B, Gajhede M. Structure of the PPX/GPPA phosphatase from Aquifex aeolicus in complex with the alarmone ppGpp. J Mol Biol. 2008;375:1469-76 pubmed publisher
    ..protein family member from Aquifex aeolicus in complex with the intracellular second messenger guanosine tetraphosphate was determined at 2.7-A resolution. The hydrolytic base is identified as E119...
  79. Hirsch M, Elliott T. Role of ppGpp in rpoS stationary-phase regulation in Escherichia coli. J Bacteriol. 2002;184:5077-87 pubmed
    ..The effect of RBS-proximal sequence was independent of all known trans-acting factors, including ppGpp...
  80. Zusman T, Gal Mor O, Segal G. Characterization of a Legionella pneumophila relA insertion mutant and toles of RelA and RpoS in virulence gene expression. J Bacteriol. 2002;184:67-75 pubmed
    ..We concluded that RelA is dispensable for intracellular growth of L. pneumophila in the two hosts examined and that both RelA and RpoS play minor roles in L. pneumophila icm/dot gene expression. ..
  81. Pomares M, Vincent P, Farias R, Salomon R. Protective action of ppGpp in microcin J25-sensitive strains. J Bacteriol. 2008;190:4328-34 pubmed publisher
    ..This would maintain the intracellular level of the antibiotic below a toxic level. ..
  82. Brown L, Gentry D, Elliott T, Cashel M. DksA affects ppGpp induction of RpoS at a translational level. J Bacteriol. 2002;184:4455-65 pubmed
    ..We propose that DksA functions downstream of ppGpp but indirectly regulates rpoS induction...
  83. Osterberg S, Sk rfstad E, Shingler V. The sigma-factor FliA, ppGpp and DksA coordinate transcriptional control of the aer2 gene of Pseudomonas putida. Environ Microbiol. 2010;12:1439-51 pubmed publisher
  84. Gummesson B, Magnusson L, Lovmar M, Kvint K, Persson O, Ballesteros M, et al. Increased RNA polymerase availability directs resources towards growth at the expense of maintenance. EMBO J. 2009;28:2209-19 pubmed publisher
    ..and damage protection; a response reminiscent of cells with no or diminished levels of the alarmone guanosine tetraphosphate (ppGpp)...
  85. Moris M, Braeken K, Schoeters E, Verreth C, Beullens S, Vanderleyden J, et al. Effective symbiosis between Rhizobium etli and Phaseolus vulgaris requires the alarmone ppGpp. J Bacteriol. 2005;187:5460-9 pubmed
    ..etli relA mutant. Our results suggest that relA may play an important role in the regulation of gene expression in R. etli bacteroids and in the adaptation of bacteroid physiology...