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Information on EC 2.7.6.5 - GTP diphosphokinase and Organism(s) Bacillus subtilis and UniProt Accession O31611
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2.7.6.5 GTP diphosphokinaseIUBMB Comments
GDP can also act as acceptor.
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Word Map
- 2.7.6.5
- pppgpp
- rela
- rsh
- tetraphosphate
-
a-site
-
actinorhodine
- mupirocin
-
ribosome-dependent
-
sass
- 3'-diphosphate
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rela-spot
- thiostrepton
-
pyrophosphorylate
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rela-dependent
- drug development
The taxonomic range for the selected organisms is: Bacillus subtilis
The enzyme appears in selected viruses and cellular organisms
The enzyme appears in selected viruses and cellular organisms
Synonyms
(p)ppgpp synthetase, stringent factor, relmtb, (p)ppgpp synthase, alarmone synthetase, gtp pyrophosphokinase, (p)ppgpp synthetase i, guanosine pentaphosphate synthetase, sas 1, atp:gtp 3'-pyrophosphotransferase, 
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topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
(p)ppGpp synthetase I
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-
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(p)ppGpp synthetase II
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-
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ATP-GTP 3'-diphosphotransferase
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-
-
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GPSI
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-
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GPSII
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-
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GTP pyrophosphokinase
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-
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guanosine 3',5'-polyphosphate synthase
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-
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guanosine 3',5'-polyphosphate synthetase
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-
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guanosine 5',3'-polyphosphate synthetase
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-
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guanosine pentaphosphate synthetase
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-
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stringent factor
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-
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-
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
ATP + GTP = AMP + guanosine 3'-diphosphate 5'-triphosphate
the catalytic pathway of (p)ppGpp synthesis involves a sequentially ordered substrate binding, activation of ATP in a strained conformation, and transfer of diphosphate through a nucleophilic substitution (SN2) reaction. pppGpp, but not ppGpp, positively regulates the enzyme at an allosteric site
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
diphosphate transfer
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-
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SYSTEMATIC NAME
IUBMB Comments
ATP:GTP 3'-diphosphotransferase
GDP can also act as acceptor.
CAS REGISTRY NUMBER
COMMENTARY
63690-89-1
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SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
guanosine 3'-diphosphate 5'-diphosphate + H2O
GDP + diphosphate
-
-
-
?
guanosine 3'-diphosphate 5'-triphosphate + H2O
GTP + diphosphate
-
-
-
?
ATP + GTP
AMP + guanosine 3'-diphosphate 5'-triphosphate
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-
-
?
ATP + GTP
AMP + guanosine 3'-diphosphate 5'-triphosphate
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-
-
?
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
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-
?
additional information
?
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-
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
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-
?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
guanosine 3'-diphosphate 5'-diphosphate + H2O
GDP + diphosphate
-
-
-
?
guanosine 3'-diphosphate 5'-triphosphate + H2O
GTP + diphosphate
-
-
-
?
ATP + GTP
AMP + guanosine 3'-diphosphate 5'-triphosphate
-
-
-
?
ATP + GTP
AMP + guanosine 3'-diphosphate 5'-triphosphate
-
-
-
?
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Mg2+
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
3
guanosine 3'-diphosphate 5'-diphosphate
pH 7.5, 37°C, recombinant enzyme
2
guanosine 3'-diphosphate 5'-triphosphate
pH 7.5, 37°C, recombinant enzyme
additional information
additional information
alarmone synthesis in SAS1 proceeds in a highly cooperative manner
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additional information
additional information
-
alarmone synthesis in SAS1 proceeds in a highly cooperative manner
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pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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
physiological function
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
physiological function
additional information
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
guanosine 3'-diphosphate 5'-triphosphate, (p)ppGpp, synthesis is required for amino acid prototrophy
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
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
-
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
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
homotetramer
domain structure and three-dimensional homology modelling, sequence comparisons, crystal structure analysis, overview
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
purified enzyme in presence of ATP and GTP, 1 week, X-ray diffraction structure determination and analysis at 2.94 A resolution
nucleotide-free Rel has an elongated conformation in which the TGS domain contacts the synthesis domain by an interface involving alpha-helix 14 and beta strands 7/8 of the synthesis and TGS domains, respectively
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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
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
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
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
additional information
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
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
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
recombinant His-tagged enzyme from Escherichia coli strain BL21(DE3) by nickel affinity chromatography and gel filtration
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
gene yjbM, recombinant expression of His-tagged enzyme in Escherichia coli strain BL21(DE3)
gene yjbM, recombinant expression of wild-type and mutant enzymes in Escherichia coli
gene relA, recombinant expression of wild-type and mutant enzymes in Escherichia coli
gene ywaC, recombinant expression of wild-type and mutant enzymes in Escherichia coli
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
CodY-independent activation of transcription of the ywaA operon, overview
the transcription factor CodY represses the ywaA operon, overview
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Kriel, A.; Brinsmade, S.R.; Tse, J.L.; Tehranchi, A.K.; Bittner, A.N.; Sonenshein, A.L.; Wang, J.D.
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.
196
189-201
2014
Bacillus subtilis (O31611), Bacillus subtilis (O54408), Bacillus subtilis (P39583), Bacillus subtilis, Bacillus subtilis 168 (O31611), Bacillus subtilis 168 (O54408), Bacillus subtilis 168 (P39583)
Steinchen, W.; Schuhmacher, J.S.; Altegoer, F.; Fage, C.D.; Srinivasan, V.; Linne, U.; Marahiel, M.A.; Bange, G.
Catalytic mechanism and allosteric regulation of an oligomeric (p)ppGpp synthetase by an alarmone
Proc. Natl. Acad. Sci. USA
112
13348-13353
2015
Bacillus subtilis (O31611), Bacillus subtilis, Bacillus subtilis 168 (O31611)
Pausch, P.; Abdelshahid, M.; Steinchen, W.; Schaefer, H.; Gratani, F.; Freibert, S.; Wolz, C.; Turgay, K.; Wilson, D.; Bange, G.
Structural basis for regulation of the opposing (p)ppGpp synthetase and hydrolase within the stringent response orchestrator rel
Cell Rep.
32
108157
2020
Bacillus subtilis (O54408), Bacillus subtilis 168 (O54408)
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