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2'-methyl-ATP + GTP
2'-methyl-AMP + guanosine 3'-diphosphate 5'-triphosphate
-
-
-
-
?
8-bromo-ATP + GTP
8-bromo-AMP + guanosine 3'-diphosphate 5'-triphosphate
-
-
-
-
?
ATP + GDP
AMP + guanosine 3',5'-bis-diphosphate
ATP + GDP
AMP + guanosine 3'-diphosphate 5'-diphosphate
ATP + GTP
AMP + guanosine 3'-diphosphate 5'-triphosphate
ATP + GTP
AMP + guanosine 5'-triphosphate 3'-diphosphate
ATP + guanosine 5'-tetraphosphate
AMP + guanosine 3'-diphosphate 5'-tetraphosphate
-
-
-
-
?
ATP + ITP
AMP + inosine 3'-diphosphate 5'-triphosphate
-
-
-
-
?
dATP + GTP
dAMP + guanosine 3'-diphosphate 5'-triphosphate
-
-
-
-
?
guanosine 3'-diphosphate 5'-diphosphate + H2O
GDP + diphosphate
guanosine 3'-diphosphate 5'-triphosphate + H2O
GTP + diphosphate
additional information
?
-
ATP + GDP
AMP + guanosine 3',5'-bis-diphosphate
-
the enzyme utilizes GDP less efficiently than GTP
-
-
?
ATP + GDP
AMP + guanosine 3',5'-bis-diphosphate
-
the enzyme utilizes GDP less efficiently than GTP
-
-
?
ATP + GDP
AMP + guanosine 3'-diphosphate 5'-diphosphate
-
-
-
?
ATP + GDP
AMP + guanosine 3'-diphosphate 5'-diphosphate
-
-
-
?
ATP + GDP
AMP + guanosine 3'-diphosphate 5'-diphosphate
-
preferred substrate
i.e ppGpp
?
ATP + GDP
AMP + guanosine 3'-diphosphate 5'-diphosphate
-
preferred substrate
-
-
?
ATP + GDP
AMP + guanosine 3'-diphosphate 5'-diphosphate
-
-
-
?
ATP + GDP
AMP + guanosine 3'-diphosphate 5'-diphosphate
-
-
-
?
ATP + GTP
AMP + guanosine 3'-diphosphate 5'-triphosphate
-
-
-
?
ATP + GTP
AMP + guanosine 3'-diphosphate 5'-triphosphate
-
-
-
?
ATP + GTP
AMP + guanosine 3'-diphosphate 5'-triphosphate
-
-
-
?
ATP + GTP
AMP + guanosine 3'-diphosphate 5'-triphosphate
-
-
-
?
ATP + GTP
AMP + guanosine 3'-diphosphate 5'-triphosphate
-
-
i.e. pppGpp
?
ATP + GTP
AMP + guanosine 3'-diphosphate 5'-triphosphate
-
-
-
-
?
ATP + GTP
AMP + guanosine 3'-diphosphate 5'-triphosphate
-
RelA-mediated guanosine 3'-diphosphate 5'-triphosphate synthesis requires the presence of an uncharged tRNAVal in the A-Site of a mRNA programmed ribosome
-
-
?
ATP + GTP
AMP + guanosine 3'-diphosphate 5'-triphosphate
-
-
-
?
ATP + GTP
AMP + guanosine 3'-diphosphate 5'-triphosphate
high degree of specificity for GTP as a pyrophosphate acceptor, with no measurable turnover for GDP
-
-
?
ATP + GTP
AMP + guanosine 3'-diphosphate 5'-triphosphate
-
-
-
-
?
ATP + GTP
AMP + guanosine 3'-diphosphate 5'-triphosphate
-
-
-
?
ATP + GTP
AMP + guanosine 3'-diphosphate 5'-triphosphate
-
-
-
?
ATP + GTP
AMP + guanosine 3'-diphosphate 5'-triphosphate
-
the enzyme uses GTP approximately twice as well as GDP
-
-
?
ATP + GTP
AMP + guanosine 3'-diphosphate 5'-triphosphate
-
the enzyme uses GTP approximately twice as well as GDP
-
-
?
ATP + GTP
AMP + guanosine 3'-diphosphate 5'-triphosphate
-
-
-
?
ATP + GTP
AMP + guanosine 3'-diphosphate 5'-triphosphate
-
-
-
?
ATP + GTP
AMP + guanosine 3'-diphosphate 5'-triphosphate
-
-
-
?
ATP + GTP
AMP + guanosine 3'-diphosphate 5'-triphosphate
-
-
-
?
ATP + GTP
AMP + guanosine 3'-diphosphate 5'-triphosphate
-
-
-
?
ATP + GTP
AMP + guanosine 3'-diphosphate 5'-triphosphate
-
-
-
?
ATP + GTP
AMP + guanosine 3'-diphosphate 5'-triphosphate
-
-
-
?
ATP + GTP
AMP + guanosine 3'-diphosphate 5'-triphosphate
-
-
-
?
ATP + GTP
AMP + guanosine 3'-diphosphate 5'-triphosphate
-
-
-
?
ATP + GTP
AMP + guanosine 3'-diphosphate 5'-triphosphate
-
-
-
?
ATP + GTP
AMP + guanosine 3'-diphosphate 5'-triphosphate
-
-
-
?
ATP + GTP
AMP + guanosine 3'-diphosphate 5'-triphosphate
-
-
-
?
ATP + GTP
AMP + guanosine 3'-diphosphate 5'-triphosphate
-
-
-
?
ATP + GTP
AMP + guanosine 3'-diphosphate 5'-triphosphate
-
-
-
?
ATP + GTP
AMP + guanosine 3'-diphosphate 5'-triphosphate
-
-
-
?
ATP + GTP
AMP + guanosine 3'-diphosphate 5'-triphosphate
-
-
-
?
ATP + GTP
AMP + guanosine 5'-triphosphate 3'-diphosphate
-
-
-
-
r
ATP + GTP
AMP + guanosine 5'-triphosphate 3'-diphosphate
-
-
-
-
r
ATP + GTP
AMP + guanosine 5'-triphosphate 3'-diphosphate
-
-
-
-
r
ATP + GTP
AMP + guanosine 5'-triphosphate 3'-diphosphate
-
bifunctional enzyme with synthetase and hydrolase activities
-
-
r
guanosine 3'-diphosphate 5'-diphosphate + H2O
GDP + diphosphate
-
-
-
?
guanosine 3'-diphosphate 5'-diphosphate + H2O
GDP + diphosphate
-
-
-
?
guanosine 3'-diphosphate 5'-diphosphate + H2O
GDP + diphosphate
-
-
-
?
guanosine 3'-diphosphate 5'-diphosphate + H2O
GDP + diphosphate
-
-
-
?
guanosine 3'-diphosphate 5'-triphosphate + H2O
GTP + diphosphate
-
-
-
?
guanosine 3'-diphosphate 5'-triphosphate + H2O
GTP + diphosphate
-
-
-
?
guanosine 3'-diphosphate 5'-triphosphate + H2O
GTP + diphosphate
-
-
-
?
guanosine 3'-diphosphate 5'-triphosphate + H2O
GTP + diphosphate
-
-
-
?
additional information
?
-
the enzyme is bifunctional showing synthase activity forming ppGpp and pppGpp, and hydrolase activity with the two compounds resulting in formation of GTP or GDP and diphosphate
-
-
?
additional information
?
-
-
the enzyme is bifunctional showing synthase activity forming ppGpp and pppGpp, and hydrolase activity with the two compounds resulting in formation of GTP or GDP and diphosphate
-
-
?
additional information
?
-
the enzyme is bifunctional showing synthase activity forming ppGpp and pppGpp, and hydrolase activity with the two compounds resulting in formation of GTP or GDP and diphosphate
-
-
?
additional information
?
-
-
no substrate: 5'(beta,gamma-imino)triphosphate, 1,N6-ethyladenosine triphosphate, no diphosphate acceptors: ATP, UTP, CTP, dGTP, dGDP, 2'-O-methyl-GDP, 7-methyl-GDP
-
-
?
additional information
?
-
-
responsible for the synthesis of guanosine 3',5'-bisdiphosphate during stringent response to amino acid starvation
-
-
?
additional information
?
-
-
(p)ppGpp synthetase II is responsible for (p)ppGpp accumulation during carbon source downshift
-
-
?
additional information
?
-
the enzyme transfers a diphosphate from ATP to GDP or GTP to synthesize guanosine 3'-diphosphate 5'-diphosphate (ppGpp) and guanosine 3'-diphosphate 5'-triphosphate (pppGpp), respectively. Enzyme RelMtb also encodes a second, distinct catalytic domain that hydrolyzes (p)ppGpp into diphosphate and GDP or GTP
-
-
?
additional information
?
-
-
the enzyme transfers a diphosphate from ATP to GDP or GTP to synthesize guanosine 3'-diphosphate 5'-diphosphate (ppGpp) and guanosine 3'-diphosphate 5'-triphosphate (pppGpp), respectively. Enzyme RelMtb also encodes a second, distinct catalytic domain that hydrolyzes (p)ppGpp into diphosphate and GDP or GTP
-
-
?
additional information
?
-
the enzyme transfers a diphosphate from ATP to GDP or GTP to synthesize guanosine 3'-diphosphate 5'-diphosphate (ppGpp) and guanosine 3'-diphosphate 5'-triphosphate (pppGpp), respectively. Enzyme RelMtb also encodes a second, distinct catalytic domain that hydrolyzes (p)ppGpp into diphosphate and GDP or GTP
-
-
?
additional information
?
-
-
the enzyme also possesses a potent Mn2+-dependent guanosine tetraphosphate hydrolysis activity, with complete hydrolysis to GDP and diphosphate
-
-
?
additional information
?
-
-
the enzyme also possesses a potent Mn2+-dependent guanosine tetraphosphate hydrolysis activity, with complete hydrolysis to GDP and diphosphate
-
-
?
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ATP + GDP
AMP + guanosine 3'-diphosphate 5'-diphosphate
ATP + GTP
AMP + guanosine 3'-diphosphate 5'-triphosphate
ATP + GTP
AMP + guanosine 5'-triphosphate 3'-diphosphate
guanosine 3'-diphosphate 5'-diphosphate + H2O
GDP + diphosphate
guanosine 3'-diphosphate 5'-triphosphate + H2O
GTP + diphosphate
additional information
?
-
ATP + GDP
AMP + guanosine 3'-diphosphate 5'-diphosphate
-
-
-
?
ATP + GDP
AMP + guanosine 3'-diphosphate 5'-diphosphate
-
-
-
?
ATP + GDP
AMP + guanosine 3'-diphosphate 5'-diphosphate
-
-
-
?
ATP + GDP
AMP + guanosine 3'-diphosphate 5'-diphosphate
-
-
-
?
ATP + GTP
AMP + guanosine 3'-diphosphate 5'-triphosphate
-
-
-
?
ATP + GTP
AMP + guanosine 3'-diphosphate 5'-triphosphate
-
-
-
?
ATP + GTP
AMP + guanosine 3'-diphosphate 5'-triphosphate
-
-
-
?
ATP + GTP
AMP + guanosine 3'-diphosphate 5'-triphosphate
-
-
-
?
ATP + GTP
AMP + guanosine 3'-diphosphate 5'-triphosphate
-
-
-
-
?
ATP + GTP
AMP + guanosine 3'-diphosphate 5'-triphosphate
-
-
-
?
ATP + GTP
AMP + guanosine 3'-diphosphate 5'-triphosphate
-
-
-
-
?
ATP + GTP
AMP + guanosine 3'-diphosphate 5'-triphosphate
-
-
-
?
ATP + GTP
AMP + guanosine 3'-diphosphate 5'-triphosphate
-
-
-
?
ATP + GTP
AMP + guanosine 5'-triphosphate 3'-diphosphate
-
-
-
-
r
ATP + GTP
AMP + guanosine 5'-triphosphate 3'-diphosphate
-
-
-
-
r
ATP + GTP
AMP + guanosine 5'-triphosphate 3'-diphosphate
-
-
-
-
r
ATP + GTP
AMP + guanosine 5'-triphosphate 3'-diphosphate
-
bifunctional enzyme with synthetase and hydrolase activities
-
-
r
guanosine 3'-diphosphate 5'-diphosphate + H2O
GDP + diphosphate
-
-
-
?
guanosine 3'-diphosphate 5'-diphosphate + H2O
GDP + diphosphate
-
-
-
?
guanosine 3'-diphosphate 5'-diphosphate + H2O
GDP + diphosphate
-
-
-
?
guanosine 3'-diphosphate 5'-diphosphate + H2O
GDP + diphosphate
-
-
-
?
guanosine 3'-diphosphate 5'-triphosphate + H2O
GTP + diphosphate
-
-
-
?
guanosine 3'-diphosphate 5'-triphosphate + H2O
GTP + diphosphate
-
-
-
?
guanosine 3'-diphosphate 5'-triphosphate + H2O
GTP + diphosphate
-
-
-
?
guanosine 3'-diphosphate 5'-triphosphate + H2O
GTP + diphosphate
-
-
-
?
additional information
?
-
-
responsible for the synthesis of guanosine 3',5'-bisdiphosphate during stringent response to amino acid starvation
-
-
?
additional information
?
-
-
(p)ppGpp synthetase II is responsible for (p)ppGpp accumulation during carbon source downshift
-
-
?
additional information
?
-
the enzyme transfers a diphosphate from ATP to GDP or GTP to synthesize guanosine 3'-diphosphate 5'-diphosphate (ppGpp) and guanosine 3'-diphosphate 5'-triphosphate (pppGpp), respectively. Enzyme RelMtb also encodes a second, distinct catalytic domain that hydrolyzes (p)ppGpp into diphosphate and GDP or GTP
-
-
?
additional information
?
-
-
the enzyme transfers a diphosphate from ATP to GDP or GTP to synthesize guanosine 3'-diphosphate 5'-diphosphate (ppGpp) and guanosine 3'-diphosphate 5'-triphosphate (pppGpp), respectively. Enzyme RelMtb also encodes a second, distinct catalytic domain that hydrolyzes (p)ppGpp into diphosphate and GDP or GTP
-
-
?
additional information
?
-
the enzyme transfers a diphosphate from ATP to GDP or GTP to synthesize guanosine 3'-diphosphate 5'-diphosphate (ppGpp) and guanosine 3'-diphosphate 5'-triphosphate (pppGpp), respectively. Enzyme RelMtb also encodes a second, distinct catalytic domain that hydrolyzes (p)ppGpp into diphosphate and GDP or GTP
-
-
?
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dCDP
slightly stimulates synthesis of guanosine 3'-diphosphate 5'-triphosphate, inhibits polynucleotide phosphorylase activities of enzyme
ethanol
-
little activity unless activated either by a complex of 70S ribosomes, mRNA and uncharged tRNA or by a solvent like ethanol at approximately 20%
guanosine-5',3'-dibisphosphate
ppGpp, potential allosteric regulator, activates the enzyme with an EC50 of 0.060 mM
methanol
-
maximal stimulation of GPSI by 20% v/v
tRNA
-
uncharged or charged, stimulation, level of stimulation is greater in presence of RNA and poly(U) together than with either RNA alone
Trypsin
-
incubation with low levels of trypsin activates
-
unacylated tRNA
-
in the ribosomal amino-acyl site (A-site)
-
mRNA
-
little activity unless activated either by a complex of 70S ribosomes, mRNA and uncharged tRNA or by a solvent like ethanol at approximately 20%
mRNA
-
(p)ppGpp synthetase II does not
mRNA
-
synthetic, e.g. poly(U), stimulates, level of stimulation is greater in presence of RNA and poly(U) together than with either RNA alone, no activation by ribosomes
additional information
-
little activity unless activated either by a complex of 70S ribosomes, mRNA and uncharged tRNA or by a solvent like ethanol at approximately 20%
-
additional information
-
addition of template, unacylated tRNA and ribosomes to the activity assay stimulates SF 30fold when using optimal conditions, activity of SF increases threefold in the presence of twice salt-washed tight-couple ribosomes and twofold in the presence of reassociated ribosomes compared to the endogenous activity of the enzyme
-
additional information
-
ribosome complexes formed with tight binding tRNAVal stimulate enzyme activity at lower concentrations than that required for ribosome complexes formed with the weaker binding tRNAPhe
-
additional information
activation of Francisella tularensis RelA by stalled ribosomal complexes formed with ribosomes purified from Escherichia coli MRE600, and significantly weaker activation with ribosomes isolated from Francisella philomiragia
-
additional information
-
(p)ppGpp synthetase II does not
-
additional information
-
no activation by ribosomes
-
additional information
-
GPS I can be activated by incubation with crude mycelial extract, activation is partially inhibited by the inclusion of trypsin inhibitor in reaction mixture
-
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Asthma
Asthma and sleep apnea in patients with morbid obesity: outcome after bariatric surgery.
Brucellosis
The stringent response mediator Rsh is required for Brucella melitensis and Brucella suis virulence, and for expression of the type IV secretion system virB.
Infections
Essential roles for Mycobacterium tuberculosis Rel beyond the production of (p)ppGpp.
Infections
Isolation of a lambda transducing bacteriophage carrying the relA gene of Escherichia coli.
Infections
Prophage-mediated defence against viral attack and viral counter-defence.
Latent Infection
The role of RelMtb-mediated adaptation to stationary phase in long-term persistence of Mycobacterium tuberculosis in mice.
Persistent Infection
Essential roles for Mycobacterium tuberculosis Rel beyond the production of (p)ppGpp.
Persistent Infection
Stringent response protein as a potential target to intervene persistent bacterial infection.
Persistent Infection
The role of RelMtb-mediated adaptation to stationary phase in long-term persistence of Mycobacterium tuberculosis in mice.
Starvation
Combinatorial stress responses: direct coupling of two major stress responses in Escherichia coli.
Starvation
Induction of cat-86 by chloramphenicol and amino acid starvation in relaxed mutants of Bacillus subtilis.
Starvation
Inhibiting the stringent response blocks Mycobacterium tuberculosis entry into quiescence and reduces persistence.
Starvation
Intramolecular Interactions Dominate the Autoregulation of Escherichia coli Stringent Factor RelA.
Starvation
Occurrence of mazEF-like antitoxin/toxin systems in bacteria.
Starvation
Regulation of Escherichia coli RelA requires oligomerization of the C-terminal domain.
Starvation
Rel Is Required for Morphogenesis of Resting Cells in Mycobacterium smegmatis.
Starvation
Stringent response of Bacillus stearothermophilus: evidence for the existence of two distinct guanosine 3',5'-polyphosphate synthetases.
Starvation
Subinhibitory Concentrations of Bacteriostatic Antibiotics Induce relA-Dependent and relA-Independent Tolerance to ?-Lactams.
Starvation
The global role of ppGpp synthesis in morphological differentiation and antibiotic production in Streptomyces coelicolor A3(2).
Starvation
The ribosome triggers the stringent response by RelA via a highly distorted tRNA.
Starvation
The stringent factor RelA adopts an open conformation on the ribosome to stimulate ppGpp synthesis.
Starvation
The stringent response is required for Helicobacter pylori survival of stationary phase, exposure to acid, and aerobic shock.
Tuberculosis
Essential roles for Mycobacterium tuberculosis Rel beyond the production of (p)ppGpp.
Tuberculosis
Functional regulation of the opposing (p)ppGpp synthetase/hydrolase activities of RelMtb from Mycobacterium tuberculosis.
Tuberculosis
Inhibiting the stringent response blocks Mycobacterium tuberculosis entry into quiescence and reduces persistence.
Tuberculosis
Mutational analysis of the (p)ppGpp synthetase activity of the Rel enzyme of Mycobacterium tuberculosis.
Tuberculosis
Stringent response protein as a potential target to intervene persistent bacterial infection.
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evolution
the enzyme belongs to the RSH superfamily, which controls concentrations of the alarmones (p)ppGpp (guanosine penta- or tetra-phosphate)
evolution
the enzyme RelA belongs to the RSH superfamily, also comprising members such as RelA/SpoT homologue, (p)ppGpp synthetase I, SpoT, and (p)ppGpp synthetase II. The RSH enzyme family controls concentrations of the alarmones (p)ppGpp (guanosine penta- or tetra-phosphate)
evolution
-
the enzyme belongs to the RSH superfamily, which controls concentrations of the alarmones (p)ppGpp (guanosine penta- or tetra-phosphate)
-
malfunction
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. Loss of the (p)ppGpp synthetase activity results in a failure of Bacillus subtilis to grow on minimal medium and causes the requirement for valine, leucine, isoleucine, threonine, and methionine, and a weaker requirement for arginine, histidine, and tryptophan addition
malfunction
Mycobacterium tuberculosis strains expressing the synthetase-dead RelMtb H344Y mutant do not persist in mice. Deletion of a second predicted (p)ppGpp synthetase has no effect on pathogenesis, demonstrating. Expression of an allele encoding the hydrolase-dead RelMtb mutant, RelMtb H80A, decreases the growth rate of Mycobacterium tuberculosis and changes the colony morphology of the bacteria. RelMtb H80A expression during acute or chronic Mycobacterium tuberculosis infection in mice is lethal to the infecting bacteria. Phenotypes, overview
malfunction
-
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. Loss of the (p)ppGpp synthetase activity results in a failure of Bacillus subtilis to grow on minimal medium and causes the requirement for valine, leucine, isoleucine, threonine, and methionine, and a weaker requirement for arginine, histidine, and tryptophan addition
-
malfunction
-
Mycobacterium tuberculosis strains expressing the synthetase-dead RelMtb H344Y mutant do not persist in mice. Deletion of a second predicted (p)ppGpp synthetase has no effect on pathogenesis, demonstrating. Expression of an allele encoding the hydrolase-dead RelMtb mutant, RelMtb H80A, decreases the growth rate of Mycobacterium tuberculosis and changes the colony morphology of the bacteria. RelMtb H80A expression during acute or chronic Mycobacterium tuberculosis infection in mice is lethal to the infecting bacteria. Phenotypes, overview
-
physiological function
guanosine 3'-diphosphate 5'-triphosphate, (p)ppGpp, synthesis is required for amino acid prototrophy
physiological function
guanosine tetraphosphate (ppGpp) and guanosine pentaphosphate (pppGpp), collectively termed (p)ppGpp, act as alarmones that globally reprogram cellular physiology during various stress conditions. Enzymes of the RelA/SpoT homology (RSH) family synthesize (p)ppGpp by transferring diphosphate from ATP to GDP or GTP. ppGpp and pppGpp execute different functional roles
physiological function
in Mycobacterium tuberculosis, the stringent response to amino acid starvation is mediated by the enzyme Rel (RelMtb), which transfers a diphosphate from ATP to GDP or GTP to synthesize guanosine 3'-diphosphate 5'-diphosphate (ppGpp) and guanosine 3'-diphosphate 5'-triphosphate (pppGpp), respectively. (p)ppGpp then influences numerous metabolic processes. RelMtb also encodes a second, distinct catalytic domain that hydrolyzes (p)ppGpp into diphosphate and GDP or GTP. RelMtb is required for chronic Mycobacterium tuberculosis infection in C57BL/6 mice. The RelMtb (p)ppGpp synthetase activity is required for maintaining bacterial titers during chronic infection, RelMtb is the major contributor to (p)ppGpp production during infection, RelMtb (p)ppGpp hydrolase activity is essential for acute and chronic infection of mice
physiological function
in vivo, under relaxed conditions, as well as in vitro, the C-terminal regulatory domain CTD inhibits synthetase activity but is not required for hydrolase activity. Under stringent conditions, the CTD is essential for (p)ppGpp synthesis. A mutant lacking the CTD exhibits net hydrolase activity when expressed in Staphylococcus aureus but net (p)ppGpp synthetase activity when expressed in Escherichia coli. The conserved TGS and DC motifs within the CTD are required for correct stringent response, whereas the conserved ACT motif is dispensable. The enzyme primarily exists in a synthetase-off/hydrolase-on state
physiological function
overexpression of isoform RSH3 cDNA in the rsh2rsh3 mutant background leads to approximately threefold higher ppGpp levels than in wild-type. Upon transition to nitrogen-deficient conditions, the mutant shows reduction of ribulose 1,5-bisphosphate carboxylase/oxygenase (RubisCO) contents, and effective and maximum quantum yield of photosystem II compared with wild-type. The mutant also shows obvious changes in key metabolite levels including some amino acid contents
physiological function
the level of ppGpp controls the length of diauxic lag via control of the level of acetyl phosphate
physiological function
-
(p)ppGpp synthetase interacts with both GTPase Era and DEAD-box RNA helicase CshA, influences the enzymatic activity of Era and CshA and is important for rRNA processing
physiological function
the Rel holoenzyme consists of the N-terminal hydrolase and synthetase domains, followed by its regulatory C-terminal domain consisting of the TGS, AH, RIS, and ACT domains. Removal of the TGS and AH subdomains leads to a pronounced increase in (p)ppGpp synthesis and a corresponding decrease in (p)ppGpp hydrolysis. Rel forms homodimers, which appear to control the interaction with deacylated-tRNA, but not the enzymatic activity of Rel
physiological function
-
guanosine 3'-diphosphate 5'-triphosphate, (p)ppGpp, synthesis is required for amino acid prototrophy
-
physiological function
-
guanosine tetraphosphate (ppGpp) and guanosine pentaphosphate (pppGpp), collectively termed (p)ppGpp, act as alarmones that globally reprogram cellular physiology during various stress conditions. Enzymes of the RelA/SpoT homology (RSH) family synthesize (p)ppGpp by transferring diphosphate from ATP to GDP or GTP. ppGpp and pppGpp execute different functional roles
-
physiological function
-
the Rel holoenzyme consists of the N-terminal hydrolase and synthetase domains, followed by its regulatory C-terminal domain consisting of the TGS, AH, RIS, and ACT domains. Removal of the TGS and AH subdomains leads to a pronounced increase in (p)ppGpp synthesis and a corresponding decrease in (p)ppGpp hydrolysis. Rel forms homodimers, which appear to control the interaction with deacylated-tRNA, but not the enzymatic activity of Rel
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physiological function
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in Mycobacterium tuberculosis, the stringent response to amino acid starvation is mediated by the enzyme Rel (RelMtb), which transfers a diphosphate from ATP to GDP or GTP to synthesize guanosine 3'-diphosphate 5'-diphosphate (ppGpp) and guanosine 3'-diphosphate 5'-triphosphate (pppGpp), respectively. (p)ppGpp then influences numerous metabolic processes. RelMtb also encodes a second, distinct catalytic domain that hydrolyzes (p)ppGpp into diphosphate and GDP or GTP. RelMtb is required for chronic Mycobacterium tuberculosis infection in C57BL/6 mice. The RelMtb (p)ppGpp synthetase activity is required for maintaining bacterial titers during chronic infection, RelMtb is the major contributor to (p)ppGpp production during infection, RelMtb (p)ppGpp hydrolase activity is essential for acute and chronic infection of mice
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additional information
mechanism and allosteric regulation of the highly cooperative enzyme from Bacillus subtilis, overview. Analysis of the catalytic mechanism of (p)ppGpp synthesis by oligomeric and highly cooperative small alarmone synthetase 1 (SAS1) at atomic resolution, structural and biochemical analysis reveals that only pppGpp, but not ppGpp, positively affects the activity of the enzyme
additional information
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mechanism and allosteric regulation of the highly cooperative enzyme from Bacillus subtilis, overview. Analysis of the catalytic mechanism of (p)ppGpp synthesis by oligomeric and highly cooperative small alarmone synthetase 1 (SAS1) at atomic resolution, structural and biochemical analysis reveals that only pppGpp, but not ppGpp, positively affects the activity of the enzyme
additional information
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mechanism and allosteric regulation of the highly cooperative enzyme from Bacillus subtilis, overview. Analysis of the catalytic mechanism of (p)ppGpp synthesis by oligomeric and highly cooperative small alarmone synthetase 1 (SAS1) at atomic resolution, structural and biochemical analysis reveals that only pppGpp, but not ppGpp, positively affects the activity of the enzyme
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D264G
site-directed mutagenesis, the mutation specifically abolishes (p)ppGpp synthetase activity without affecting other potential functions of the protein. Loss of the (p)ppGpp synthetase activity results in failure to grow on minimal medium and requirement for valine, leucine, isoleucine, threonine, and methionine, and a weaker requirement for arginine, histidine, and tryptophan addition
D72G
site-directed mutagenesis, the mutation specifically abolishes (p)ppGpp synthetase activity without affecting other potential functions of the protein. Loss of the (p)ppGpp synthetase activity results in failure to grow on minimal medium and requirement for valine, leucine, isoleucine, threonine, and methionine, and a weaker requirement for arginine, histidine, and tryptophan addition
D87G
site-directed mutagenesis, the mutation specifically abolishes (p)ppGpp synthetase activity without affecting other potential functions of the protein. Loss of the (p)ppGpp synthetase activity results in failure to grow on minimal medium and requirement for valine, leucine, isoleucine, threonine, and methionine, and a weaker requirement for arginine, histidine, and tryptophan addition
E324V
inactive in (p)ppGpp synthesis
G283E
mutation is located at the interface of synthesis domain and TGS domain. Mutant is deregulated, showing high (p)ppGpp synthetic and reduced (p)ppGpp hydrolytic activity
Y279E
mutation is located at the interface of synthesis domain and TGS domain. Mutant is inactive in (p)ppGpp synthesis in vitro, but not in vivo
D264G
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site-directed mutagenesis, the mutation specifically abolishes (p)ppGpp synthetase activity without affecting other potential functions of the protein. Loss of the (p)ppGpp synthetase activity results in failure to grow on minimal medium and requirement for valine, leucine, isoleucine, threonine, and methionine, and a weaker requirement for arginine, histidine, and tryptophan addition
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D72G
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site-directed mutagenesis, the mutation specifically abolishes (p)ppGpp synthetase activity without affecting other potential functions of the protein. Loss of the (p)ppGpp synthetase activity results in failure to grow on minimal medium and requirement for valine, leucine, isoleucine, threonine, and methionine, and a weaker requirement for arginine, histidine, and tryptophan addition
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D87G
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site-directed mutagenesis, the mutation specifically abolishes (p)ppGpp synthetase activity without affecting other potential functions of the protein. Loss of the (p)ppGpp synthetase activity results in failure to grow on minimal medium and requirement for valine, leucine, isoleucine, threonine, and methionine, and a weaker requirement for arginine, histidine, and tryptophan addition
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E324V
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inactive in (p)ppGpp synthesis
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G283E
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mutation is located at the interface of synthesis domain and TGS domain. Mutant is deregulated, showing high (p)ppGpp synthetic and reduced (p)ppGpp hydrolytic activity
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Y279E
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mutation is located at the interface of synthesis domain and TGS domain. Mutant is inactive in (p)ppGpp synthesis in vitro, but not in vivo
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E319Q
mutant lacks (p)ppGpp synthase activity but retains hydrolase activity
C633A
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20fold decrease in activity
D632A
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3.5fold decrease in activity
D81A
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loss of hydrolytic activity with retention of synthesis
G241E
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loss of synthetic activity and retention of hydrolysis
H344Y
-
site-directed mutagenesis, the mutant enzyme shows no synthase activity
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H80A
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site-directed mutagenesis, the mutant enzyme shows no hydrolase activity
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D264G
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eliminates detectable synthetase activity without appreciably altering the hydrolase activity
E323Q
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eliminates detectable synthetase activity without appreciably altering the hydrolase activity
H344Y
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loss of synthetic activity and retention of hydrolysis
H344Y
site-directed mutagenesis, the mutant enzyme shows no synthase activity
H80A
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loss of hydrolytic activity with retention of synthesis
H80A
site-directed mutagenesis, the mutant enzyme shows no hydrolase activity
additional information
generation of strain JDW1464 (relAD264G ywaCD87GyjbMD72G) by substituting a conserved aspartic acid residue in each of the three (p)ppGpp synthetases, corresponding to D264 in RelA, D87 in YwaC, and D72 in YjbM, with glycine
additional information
generation of strain JDW1464 (relAD264G ywaCD87GyjbMD72G) by substituting a conserved aspartic acid residue in each of the three (p)ppGpp synthetases, corresponding to D264 in RelA, D87 in YwaC, and D72 in YjbM, with glycine
additional information
generation of strain JDW1464 (relAD264G ywaCD87GyjbMD72G) by substituting a conserved aspartic acid residue in each of the three (p)ppGpp synthetases, corresponding to D264 in RelA, D87 in YwaC, and D72 in YjbM, with glycine
additional information
-
generation of strain JDW1464 (relAD264G ywaCD87GyjbMD72G) by substituting a conserved aspartic acid residue in each of the three (p)ppGpp synthetases, corresponding to D264 in RelA, D87 in YwaC, and D72 in YjbM, with glycine
additional information
-
generation of strain JDW1464 (relAD264G ywaCD87GyjbMD72G) by substituting a conserved aspartic acid residue in each of the three (p)ppGpp synthetases, corresponding to D264 in RelA, D87 in YwaC, and D72 in YjbM, with glycine
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additional information
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fragments 1-203 (22.7 kDa) and 1-181 (20.1 kDa) possess hydrolytic activity but are incapable of synthesis activity, fragment 1-156 (17.3 kDa) is not capable of either synthesis or hydolytic activity, relative acticity of fragment 1-181 decreases approximately 130fold compared to that of the wild type, fragment 87-394 (35.1 kDa) has only synthesis activity, fragment 1-394 (44.6 kDa) and 1-450 are capable of synthesis and hydrolysis, the trimer state of fragment 1-394 appears to be a catalytically less efficient state than the monomer state, fragment 395-738 is devoid of any activity
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Functional Regulation of the Opposing (p)ppGpp Synthetase/Hydrolase Activities of RelMtb from Mycobacterium tuberculosis
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