guanosine pentaphosphate


Summary: Guanosine 5'-triphosphate 2'(3')-diphosphate. A guanine nucleotide containing five phosphate groups. Three 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 II.

Top Publications

  1. Hogg T, Mechold U, Malke H, Cashel M, Hilgenfeld R. Conformational antagonism between opposing active sites in a bifunctional RelA/SpoT homolog modulates (p)ppGpp metabolism during the stringent response [corrected]. Cell. 2004;117:57-68 pubmed
    ..Reciprocal regulation of the antagonistic catalytic activities, suggested by the structure, is supported by mutagenesis experiments and appears to involve ligand-induced signal transmission between the two active sites...
  2. Lemos J, Nascimento M, Lin V, Abranches J, Burne R. Global regulation by (p)ppGpp and CodY in Streptococcus mutans. J Bacteriol. 2008;190:5291-9 pubmed publisher
    ..Notably, the identification of putative CodY-binding boxes upstream of genes that were downregulated in the codY mutant indicates that CodY may also function as a transcriptional activator in S. mutans...
  3. 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. ..
  4. 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. ..
  5. Wehmeier L, Brockmann Gretza O, Pisabarro A, Tauch A, P hler A, Martin J, et al. A Corynebacterium glutamicum mutant with a defined deletion within the rplK gene is impaired in (p)ppGpp accumulation upon amino acid starvation. Microbiology. 2001;147:691-700 pubmed publisher
    ..Evidently, the C. glutamicum rplK gene is required for (p)ppGpp accumulation upon nutritional starvation...
  6. Primm T, Andersen S, Mizrahi V, Avarbock D, Rubin H, Barry C. The stringent response of Mycobacterium tuberculosis is required for long-term survival. J Bacteriol. 2000;182:4889-98 pubmed
    ..Thus, the Rel(Mtb) protein is required for long-term survival of pathogenic mycobacteria under starvation conditions. ..
  7. Braeken K, Moris M, Daniels R, Vanderleyden J, Michiels J. New horizons for (p)ppGpp in bacterial and plant physiology. Trends Microbiol. 2006;14:45-54 pubmed
    ..Recently, there have been several new discoveries about the effects of (p)ppGpp levels, balanced by RelA-SpoT homologue proteins, in diverse organisms. ..
  8. 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. ..
  9. Choi M, Wang Y, Wong L, Lu B, Chen W, Huang J, et al. The two PPX-GppA homologues from Mycobacterium tuberculosis have distinct biochemical activities. PLoS ONE. 2012;7:e42561 pubmed publisher
    Inorganic polyphosphate (poly-P), guanosine pentaphosphate (pppGpp) and guanosine tetraphosphate (ppGpp) are ubiquitous in bacteria...

More Information


  1. 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. ..
  2. Keasling J, Bertsch L, Kornberg A. Guanosine pentaphosphate phosphohydrolase of Escherichia coli is a long-chain exopolyphosphatase. Proc Natl Acad Sci U S A. 1993;90:7029-33 pubmed
    ..The second exopoly(P)ase has now been identified as guanosine pentaphosphate phosphohydrolase (GPP; EC 3.6.1...
  3. Kazmierczak K, Wayne K, Rechtsteiner A, Winkler M. Roles of rel(Spn) in stringent response, global regulation and virulence of serotype 2 Streptococcus pneumoniae D39. Mol Microbiol. 2009;72:590-611 pubmed publisher
    ..Finally, a D39 Deltarel(Spn) mutant was severely attenuated and displayed a significantly altered course of disease progression in a mouse model of infection, which was restored to normal by an ectopic copy of rel(+)(Spn)...
  4. 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. ..
  5. 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. ..
  6. 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
  7. 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
    The crystal structure of the prototype exopolyphosphatase/guanosine pentaphosphate phosphohydrolase protein family member from Aquifex aeolicus in complex with the intracellular second messenger guanosine tetraphosphate was determined at ..
  8. 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)...
  9. 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. ..
  10. 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. ..
  11. Dean R, Ireland P, Jordan J, Titball R, Oyston P. RelA regulates virulence and intracellular survival of Francisella novicida. Microbiology. 2009;155:4104-13 pubmed publisher
    ..Therefore, (p)ppGpp appears to be an important intracellular signal, integral to the pathogenesis of F. novicida. ..
  12. Cassels R, Oliva B, Knowles D. Occurrence of the regulatory nucleotides ppGpp and pppGpp following induction of the stringent response in staphylococci. J Bacteriol. 1995;177:5161-5 pubmed
    ..Spots corresponding to ppGpp and pppGpp on thin-layer chromatograms suggest that pppGpp is the principal regulatory nucleotide synthesized by staphylococci in response to mupirocin, rather than ppGpp as in E. coli. ..
  13. Pesavento C, Hengge R. Bacterial nucleotide-based second messengers. Curr Opin Microbiol. 2009;12:170-6 pubmed publisher
    ..Moreover, recent advances in c-di-GMP-mediated signaling will be presented and the integration of c-di-GMP signaling with other nucleotide-based signaling systems will be discussed. ..
  14. Wu J, Xie J. Magic spot: (p) ppGpp. J Cell Physiol. 2009;220:297-302 pubmed publisher
    ..Therefore, more attention should be focused on the molecular mechanisms of (p) ppGpp, as it is the foundation to understanding how bacteria adapt to extreme circumstances through the stringent response. ..
  15. 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. ..
  16. Concepcion M, Nelson D. Expression of spoT in Borrelia burgdorferi during serum starvation. J Bacteriol. 2003;185:444-52 pubmed
    ..coli CF1693. The data suggest that B. burgdorferi exhibits a stringent response to serum starvation and during incubation in tick saliva. ..
  17. Tehranchi A, Blankschien M, Zhang Y, Halliday J, Srivatsan A, Peng J, et al. The transcription factor DksA prevents conflicts between DNA replication and transcription machinery. Cell. 2010;141:595-605 pubmed publisher
    ..We conclude that transcription elongation factors alleviate fundamental conflicts between replication and transcription, thereby protecting replication fork progression and DNA integrity. ..
  18. Adebali O, Sancar A, Selby C. Mfd translocase is necessary and sufficient for transcription-coupled repair in Escherichia coli. J Biol Chem. 2017;292:18386-18391 pubmed publisher a second pathway ("backtracking-mediated TCR") that is dependent on the UvrD helicase and the guanosine pentaphosphate (ppGpp) alarmone/stringent response regulator...
  19. Geiger T, Goerke C, Fritz M, Schäfer T, Ohlsen K, Liebeke M, et al. Role of the (p)ppGpp synthase RSH, a RelA/SpoT homolog, in stringent response and virulence of Staphylococcus aureus. Infect Immun. 2010;78:1873-83 pubmed publisher
    ..These results indicate that stringent conditions are present during infection and that RSH-dependent derepression of CodY-regulated genes is essential for virulence in S. aureus. ..
  20. Bittner A, Kriel A, Wang J. Lowering GTP level increases survival of amino acid starvation but slows growth rate for Bacillus subtilis cells lacking (p)ppGpp. J Bacteriol. 2014;196:2067-76 pubmed publisher
  21. Tian C, Semsey S, Mitarai N. Synchronized switching of multiple toxin-antitoxin modules by (p)ppGpp fluctuation. Nucleic Acids Res. 2017;45:8180-8189 pubmed publisher
    ..The duration of the high (p)ppGpp state was found to be the key parameter for persistence. The (p)ppGpp-driven synchronized transition of all TA systems results in the redundancy. ..
  22. Mechold U, Potrykus K, Murphy H, Murakami K, Cashel M. Differential regulation by ppGpp versus pppGpp in Escherichia coli. Nucleic Acids Res. 2013;41:6175-89 pubmed publisher
    ..coli RNA polymerase-?(70) holoenzyme with ppGpp and pppGpp. We find that both nucleotides bind to a site at the interface between ?' and ? subunits. ..
  23. VandenBerg K, Ahn S, Visick J. (p)ppGpp-Dependent Persisters Increase the Fitness of Escherichia coli Bacteria Deficient in Isoaspartyl Protein Repair. Appl Environ Microbiol. 2016;82:5444-54 pubmed publisher
    ..High-level persister formation in the Δpcm ΔglpD mutant was dependent on guanosine pentaphosphate [(p)ppGpp] and polyphosphate...
  24. Steinchen W, Schuhmacher J, Altegoer F, Fage C, Srinivasan V, Linne U, et al. Catalytic mechanism and allosteric regulation of an oligomeric (p)ppGpp synthetase by an alarmone. Proc Natl Acad Sci U S A. 2015;112:13348-53 pubmed publisher
    ..In bacteria and plant chloroplasts, guanosine tetraphosphate (ppGpp) and guanosine pentaphosphate (pppGpp) [collectively named "(p)ppGpp"] act as alarmones that globally reprogram cellular physiology ..
  25. Rao N, Liu S, Kornberg A. Inorganic polyphosphate in Escherichia coli: the phosphate regulon and the stringent response. J Bacteriol. 1998;180:2186-93 pubmed
    ..Hence, accumulation of polyP requires a functional phoB gene and elevated levels of (p)ppGpp. A rapid assay of polyP depends on its adsorption to an anion-exchange disk on which it is hydrolyzed by a yeast exopolyphosphatase. ..
  26. Syal K, Chatterji D. Differential binding of ppGpp and pppGpp to E. coli RNA polymerase: photo-labeling and mass spectral studies. Genes Cells. 2015;20:1006-16 pubmed publisher
    ..The competition between tetraphosphate guanosine and pentaphosphate guanosine for E. coli RNA polymerase was followed by gel-based assay as well as by a new method known as DRaCALA assay. ..
  27. Stella A, Luz Hessel DA Cunha D, Piazza R, Spira B. ppGpp and cytotoxicity diversity in Shiga toxin-producing Escherichia coli (STEC) isolates. Epidemiol Infect. 2017;145:2204-2211 pubmed publisher
    ..All but two stx2 isolates belonged to the stx2b subtype. Strains that belonged to phylogroup B1 displayed on average low levels of ppGpp and high cytotoxicity. Overall, there was a negative correlation between cytotoxicity and ppGpp. ..
  28. Denapoli J, Tehranchi A, Wang J. Dose-dependent reduction of replication elongation rate by (p)ppGpp in Escherichia coli and Bacillus subtilis. Mol Microbiol. 2013;88:93-104 pubmed publisher
    ..subtilis. This supports a model where replication elongation rates are regulated by (p)ppGpp to allow rapid and tunable response to multiple abrupt stresses in evolutionarily diverse bacteria. ..
  29. Merrikh H, Ferrazzoli A, Lovett S. Growth phase and (p)ppGpp control of IraD, a regulator of RpoS stability, in Escherichia coli. J Bacteriol. 2009;191:7436-46 pubmed publisher
    ..Our results suggest that the induction of RpoS during transition to stationary phase and by (p)ppGpp occurs at least partially through IraD. ..
  30. Drecktrah D, Lybecker M, Popitsch N, Rescheneder P, Hall L, Samuels D. The Borrelia burgdorferi RelA/SpoT Homolog and Stringent Response Regulate Survival in the Tick Vector and Global Gene Expression during Starvation. PLoS Pathog. 2015;11:e1005160 pubmed publisher
    ..burgdorferi in vitro increased the levels of guanosine tetraphosphate (ppGpp) and guanosine pentaphosphate (pppGpp), collectively referred to as (p)ppGpp, products of the bifunctional synthetase/hydrolase RelBbu (..
  31. Yamanaka K, Inouye M. Growth-phase-dependent expression of cspD, encoding a member of the CspA family in Escherichia coli. J Bacteriol. 1997;179:5126-30 pubmed
    ..Moreover, the expression of cspD is inversely dependent on growth rates and induced upon glucose starvation. Using a (p)ppGpp-depleted strain, we found that (p)ppGpp is one of the positive factors for the regulation of cspD expression. ..
  32. Chiuchiolo M, Delgado M, Farias R, Salomon R. Growth-phase-dependent expression of the cyclopeptide antibiotic microcin J25. J Bacteriol. 2001;183:1755-64 pubmed
    ..Measurements of microcin J25 production by strains defective in these global regulators showed a good correlation with the reduced expression of the fusions in such mutant backgrounds. ..
  33. Itikawa H, Fujita H, Wada M. High temperature induction of a stringent response in the dnaK(Ts) and dnaJ(Ts) mutants of Escherichia coli. J Biochem. 1986;99:1719-24 pubmed
    ..5 mM, respectively. This unusual accumulation of ppGpp was suppressed by the relA1 mutation, implying that it results from induction of a stringent response in these mutants at a nonpermissive temperature. ..
  34. Ruffing A, Chen R. Transcriptome profiling of a curdlan-producing Agrobacterium reveals conserved regulatory mechanisms of exopolysaccharide biosynthesis. Microb Cell Fact. 2012;11:17 pubmed publisher
    ..Furthermore, many of the genes identified in this study are highly conserved across microbial genomes, and we propose that the molecular elements identified in this study may serve as universal regulators of microbial EPS synthesis. ..
  35. Rhee H, Lee C, Cho S, Song M, Cashel M, Choy H, et al. Selective fluorescent chemosensor for the bacterial alarmone (p)ppGpp. J Am Chem Soc. 2008;130:784-5 pubmed publisher
    ..By using pyrene-excimer fluorescence, PyDPA shows very good selectivity for (p)ppGpp from among other nucleotides in water. PyDPA was used for the real-time detection of in vitro ppGpp synthesis by bacterial ribosomal complexes. ..
  36. Vogt S, Green C, Stevens K, Day B, Erickson D, Woods D, et al. The stringent response is essential for Pseudomonas aeruginosa virulence in the rat lung agar bead and Drosophila melanogaster feeding models of infection. Infect Immun. 2011;79:4094-104 pubmed publisher
    ..Our results indicate that the stringent response, and SpoT in particular, is a crucial regulator of virulence processes in P. aeruginosa...
  37. Colomer Winter C, Gaca A, Lemos J. Association of Metal Homeostasis and (p)ppGpp Regulation in the Pathophysiology of Enterococcus faecalis. Infect Immun. 2017;85: pubmed publisher
    ..faecalis and beyond. ..
  38. Geng X, Li W, Chen Z, Gao S, Hong W, Ge X, et al. The Bifunctional Enzyme SpoT Is Involved in the Clarithromycin Tolerance of Helicobacter pylori by Upregulating the Transporters HP0939, HP1017, HP0497, and HP0471. Antimicrob Agents Chemother. 2017;61: pubmed publisher
    ..Taken together, our results revealed a novel molecular mechanism of H. pylori adaption to CLA stress. ..
  39. Yamada A, Tsutsumi K, Tanimoto S, Ozeki Y. Plant RelA/SpoT homolog confers salt tolerance in Escherichia coli and Saccharomyces cerevisiae. Plant Cell Physiol. 2003;44:3-9 pubmed
    ..In E. coli, RelA/SpoT controlled the amount of guanosine tetraphosphate (ppGpp) and guanosine pentaphosphate (pppGpp), which are the effectors of the bacterial stringent response...
  40. Wendrich T, Beckering C, Marahiel M. Characterization of the relA/spoT gene from Bacillus stearothermophilus. FEMS Microbiol Lett. 2000;190:195-201 pubmed
    ..stearothermophilus presumed to serve also as (p)ppGpp hydrolase. ..
  41. 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. ..
  42. Gourse R, Gaal T, Bartlett M, Appleman J, Ross W. rRNA transcription and growth rate-dependent regulation of ribosome synthesis in Escherichia coli. Annu Rev Microbiol. 1996;50:645-77 pubmed
    ..The mechanisms contributing to rRNA transcription work together and compensate for one another when individual systems are rendered inoperative. ..
  43. Belitskiĭ B, Shakulov R. [Role of spot gene product in the degradation of pppGpp in bacteria]. Mol Biol (Mosk). 1982;16:857-64 pubmed
    ..subtilis cells the product of gpp gene is missing or has low activity. ..
  44. Das B, Pal R, Bag S, Bhadra R. Stringent response in Vibrio cholerae: genetic analysis of spoT gene function and identification of a novel (p)ppGpp synthetase gene. Mol Microbiol. 2009;72:380-98 pubmed publisher
    ..Analysis of a V. choleraeDeltarelADeltaspoTDeltarelV triple mutant confirmed that apart from canonical relA and spoT genes, relV is a novel gene in V. cholerae responsible for (p)ppGpp synthesis...
  45. Boes N, Schreiber K, Schobert M. SpoT-triggered stringent response controls usp gene expression in Pseudomonas aeruginosa. J Bacteriol. 2008;190:7189-99 pubmed publisher
    ..Additional investigation of stationary phase in LB medium revealed that alkaline pH values are involved in the regulatory process of ppGpp accumulation...
  46. Natori Y, Tagami K, Murakami K, Yoshida S, Tanigawa O, Moh Y, et al. Transcription activity of individual rrn operons in Bacillus subtilis mutants deficient in (p)ppGpp synthetase genes, relA, yjbM, and ywaC. J Bacteriol. 2009;191:4555-61 pubmed publisher
  47. Knauber T, Doss S, Gerth K, Perlova O, Muller R, Treuner Lange A. Mutation in the rel gene of Sorangium cellulosum affects morphological and physiological differentiation. Mol Microbiol. 2008;69:254-66 pubmed publisher
    ..This induction does not occur in the rel mutant. The rel mutant also lost the capability to form multicellular fruiting bodies under nutrient starvation. ..
  48. Fischer M, Zimmerman T, Short S. A rapid method for the determination of guanosine 5'-diphosphate-3'-diphosphate and guanosine 5'-triphosphate-3'-diphosphate by high-performance liquid chromatography. Anal Biochem. 1982;121:135-9 pubmed
  49. Okada Y, Makino S, Tobe T, Okada N, Yamazaki S. Cloning of rel from Listeria monocytogenes as an osmotolerance involvement gene. Appl Environ Microbiol. 2002;68:1541-7 pubmed
    ..had very high homology to relA of Bacillus subtilis, which encodes guanosine tetraphosphate (ppGpp) and guanosine pentaphosphate (pppGpp) [collectively designated (p)ppGpp] synthetase during stringent response...
  50. 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...
  51. Kriel A, Brinsmade S, Tse J, Tehranchi A, Bittner A, Sonenshein A, et al. GTP dysregulation in Bacillus subtilis cells lacking (p)ppGpp results in phenotypic amino acid auxotrophy and failure to adapt to nutrient downshift and regulate biosynthesis genes. J Bacteriol. 2014;196:189-201 pubmed publisher
    ..This ability of (p)ppGpp to integrate a general stress response with a targeted reprogramming of gene regulation allows appropriate adaptation and is likely conserved among diverse bacteria. ..
  52. Chavez de Paz L, LEMOS J, Wickström C, Sedgley C. Role of (p)ppGpp in biofilm formation by Enterococcus faecalis. Appl Environ Microbiol. 2012;78:1627-30 pubmed publisher
    ..E. faecalis lacking (p)ppGpp had a diminished capacity to sustain biofilm formation over an extended period of time and expressed abundant proteolytic activity. ..
  53. Gomez Escribano J, Martin J, Hesketh A, Bibb M, Liras P. Streptomyces clavuligerus relA-null mutants overproduce clavulanic acid and cephamycin C: negative regulation of secondary metabolism by (p)ppGpp. Microbiology. 2008;154:744-55 pubmed publisher
  54. O Farrell P. The suppression of defective translation by ppGpp and its role in the stringent response. Cell. 1978;14:545-57 pubmed
    ..In addition, the direct and specific effects of ppGpp on gene expression are examined independently of amino acid starvation. ..
  55. Singer M, Kaiser D. Ectopic production of guanosine penta- and tetraphosphate can initiate early developmental gene expression in Myxococcus xanthus. Genes Dev. 1995;9:1633-44 pubmed
    ..These results suggest that M. xanthus cells can assess their nutritional status by monitoring the internal availability of amino acids through (p)ppGpp levels. ..
  56. 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. ..
  57. Jiang M, Sullivan S, Wout P, Maddock J. G-protein control of the ribosome-associated stress response protein SpoT. J Bacteriol. 2007;189:6140-7 pubmed
    ..Intriguingly, we found that in the absence of spoT and relA, cgtA is still an essential gene in Escherichia coli. ..
  58. Zhang P, Wang Y, Chang Y, Xiong Z, Huang C. Highly selective detection of bacterial alarmone ppGpp with an off-on fluorescent probe of copper-mediated silver nanoclusters. Biosens Bioelectron. 2013;49:433-7 pubmed publisher
  59. Vachova L, Strnadova M, Kucerova H, Chaloupka J. Effect of actinomycin D on viability, sporulation and nucleotide pool of Bacillus megaterium. Folia Microbiol (Praha). 1990;35:190-9 pubmed
    ..The ability of sporulation was, however, markedly limited. The share of cells that could sporulate increased when the irreversible sporulation phase was reached. ..
  60. 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) ..
  61. Wendrich T, Marahiel M. Cloning and characterization of a relA/spoT homologue from Bacillus subtilis. Mol Microbiol. 1997;26:65-79 pubmed
  62. Das B, Bhadra R. Molecular characterization of vibrio cholerae DeltarelA DeltaspoT double mutants. Arch Microbiol. 2008;189:227-38 pubmed publisher
    ..Since these phenotypes of DeltarelA DeltaspoT mutants could be reverted back to DeltarelA phenotypes by providing SpoT in trans, it appears that the spoT gene function is crucial in V. cholerae...
  63. Lemos J, Lin V, Nascimento M, Abranches J, Burne R. Three gene products govern (p)ppGpp production by Streptococcus mutans. Mol Microbiol. 2007;65:1568-81 pubmed publisher
  64. Berthon J, Fujikane R, Forterre P. When DNA replication and protein synthesis come together. Trends Biochem Sci. 2009;34:429-34 pubmed publisher
    ..We believe that this gene organization is biologically relevant and, moreover, that it suggests the existence of a mechanism coupling DNA replication and translation in Archaea and Eukarya. ..
  65. Wu J, Long Q, Xie J. (p)ppGpp and drug resistance. J Cell Physiol. 2010;224:300-4 pubmed publisher
    ..The accumulation of alarmones guanosine tetraphosphate and guanosine pentaphosphate, collectively known as (p)ppGpp, is a global response of bacteria to environmental stress...
  66. Jones P, Cashel M, Glaser G, Neidhardt F. Function of a relaxed-like state following temperature downshifts in Escherichia coli. J Bacteriol. 1992;174:3903-14 pubmed
    ..Our results indicate that the previously reported decrease in the (p)ppGpp level following temperature downshift plays a physiological role in the regulation of gene expression and adaptation for growth at low temperature. ..
  67. Ning D, Qian Y, Miao X, Wen C. Role of the all1549 (ana-rsh) gene, a relA/spoT homolog, of the Cyanobacterium Anabaena sp. PCC7120. Curr Microbiol. 2011;62:1767-73 pubmed publisher
    ..pcc7120. ..
  68. Bergmiller T, Pena Miller R, Boehm A, Ackermann M. Single-cell time-lapse analysis of depletion of the universally conserved essential protein YgjD. BMC Microbiol. 2011;11:118 pubmed publisher
  69. Takata R, Isaksson L. The temperature sensitive mutant 72c. II. Accumulation at high temperature of ppGpp and pppGpp in the presence of protein synthesis. Mol Gen Genet. 1978;161:15-21 pubmed
    ..In addition, the relative amounts of the two forms of ribosomal protein S6, which can be obtained on DEAE chromatography (Held et al., 1973), are significantly changed in the mutant. ..
  70. van der Biezen E, Sun J, Coleman M, Bibb M, Jones J. Arabidopsis RelA/SpoT homologs implicate (p)ppGpp in plant signaling. Proc Natl Acad Sci U S A. 2000;97:3747-52 pubmed
    ..In Escherichia coli, RelA and SpoT determine the level of guanosine tetraphosphate (ppGpp) and guanosine pentaphosphate (pppGpp), which are the effector nucleotides of the bacterial stringent response...
  71. Hwang J, Inouye M. RelA functionally suppresses the growth defect caused by a mutation in the G domain of the essential Der protein. J Bacteriol. 2008;190:3236-43 pubmed publisher
    ..This is the first demonstration of suppression of impaired function of Der by a functional enzyme. A possible mechanism of the suppression of DerN321D by RelA overproduction is discussed. ..
  72. Haralalka S, Nandi S, Bhadra R. Mutation in the relA gene of Vibrio cholerae affects in vitro and in vivo expression of virulence factors. J Bacteriol. 2003;185:4672-82 pubmed
  73. Knutsson Jenvert R, Holmberg Schiavone L. Characterization of the tRNA and ribosome-dependent pppGpp-synthesis by recombinant stringent factor from Escherichia coli. FEBS J. 2005;272:685-95 pubmed
    ..However, tRNA-saturation curves, performed at two different ribosome/stringent factor ratios and filter-binding assays, did not support this hypothesis. ..
  74. Maisonneuve E, Castro Camargo M, Gerdes K. (p)ppGpp controls bacterial persistence by stochastic induction of toxin-antitoxin activity. Cell. 2013;154:1140-1150 pubmed publisher
    ..p)ppGpp triggers slow growth by activating toxin-antitoxin loci through a regulatory cascade depending on inorganic polyphosphate and Lon protease. ..
  75. Silva A, Benitez J. A Vibrio cholerae relaxed (relA) mutant expresses major virulence factors, exhibits biofilm formation and motility, and colonizes the suckling mouse intestine. J Bacteriol. 2006;188:794-800 pubmed
    ..Nevertheless, overexpression of RelA protein from an isopropyl-beta-d-thiogalactopyranoside-inducible promoter posttranscriptionally diminished production of HA/protease. ..
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    ..2007) show that (p)ppGpp also inhibits DNA replication elongation by interfering with DNA primase activity. Halting replication may help cells to maintain genomic integrity during periods of transient nutrient limitation. ..
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    ..clavuligerus and that RelA primarily governs the stringent response of S. clavuligerus to starvation for amino acids. ..
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    ..We speculate that the observed inhibition in vitro may reflect a role of ppGpp in the regulation of antibiotic production in vivo. ..
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    ..A thoughtful comparative structural analysis provides important insights into the chemical mechanism of primase. ..