6.3.4.2: CTP synthase (glutamine hydrolysing)
This is an abbreviated version!
For detailed information about CTP synthase (glutamine hydrolysing), go to the full flat file.
Word Map on EC 6.3.4.2
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6.3.4.2
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pyrimidine
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cytosine
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cytoophidia
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dctp
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cyclopentenyl
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deoxycytidine
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acivicin
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glutamine-dependent
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3-deazauridine
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rheumatology
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l-glutamine
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alliance
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carra
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ctpas
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pyrazofurin
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uridine-cytidine
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rheumatologist
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6-diazo-5-oxo-l-norleucine
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drug development
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medicine
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analysis
- 6.3.4.2
- pyrimidine
- cytosine
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cytoophidia
- dctp
-
cyclopentenyl
- deoxycytidine
- acivicin
-
glutamine-dependent
- 3-deazauridine
-
rheumatology
- l-glutamine
-
alliance
-
carra
-
ctpas
- pyrazofurin
-
uridine-cytidine
-
rheumatologist
- 6-diazo-5-oxo-l-norleucine
- drug development
- medicine
- analysis
Reaction
Synonyms
CTP synthase, CTP synthase 1, CTP synthetase, CTP synthetase 1, CTPS, CTPS1, CTPS2, CTPsyn, CTS, cytidine 5'-triphosphate synthase, cytidine 5'-triphosphate synthetase, cytidine triphosphate synthetase, cytidine triphosphate synthetase 1, EcCTPS, pfCTP synthetase, PyrG, synthetase, cytidine triphosphate, URA7, uridine triphosphate aminase, UTP-ammonia ligase, UTP:ammonia ligase (ADP-forming)
ECTree
6.3.4.2 CTP synthase (glutamine hydrolysing)Advanced search results
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results (Inhibitors
Inhibitors on EC 6.3.4.2 - CTP synthase (glutamine hydrolysing)
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INHIBITOR 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
IMAGE
2',3'-dialdehyde adenosine 5'-triphosphate
irreversible inhibitor of CTPS
2'-deoxy-GTP
no guanosine, kact: 1.5/sec, KA: 0.21 mM, Ki: 0.36 mM; the GTP analogue is capable of inhibiting Gln-dependent CTP formation at over 0.15 mM
6-thio-GTP
the GTP analogue is capable of inhibiting Gln-dependent CTP formation at over 0.15 mM
6-thioguanosine 5'-triphosphate
no guanosine, kact: 8.5/sec, KA: 0.035 mM, Ki: 0.27 mM
acivicin
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irreversible inhibition by the glutamine analogue acivin. The acivicin inhibition of Trypanosoma brucei CTPS is more pronounced when the enzyme is preincubated with the drug in the presence of nucleotide substrates than in the absence of substrates
adenosine 5'-[beta,gamma-imido]triphosphate
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poor inhibitor compared to ATPgammaS
alpha-amino-3-chloro-4,5-dihydro-5-isoxazoleacetic acid
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reduces the parasite CTP level even further and inhibits trypanosome proliferation in vitro and in Trypanosoma brucei-infected mice
Cu2+
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inhibition is not reversed by EDTA, in presence of dithiothreitol inhibition at concentrations below 0.2 mM
DL-DELTA1-pyrroline 5-carboxylate
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0.125 mM, complete inhibition of ammonium chloride-dependent CTP synthesis
Gln
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inhibition of hydroxylamine-dependent N4-OH CTP synthesis in presence of GTP
glutamate gamma-semialdehyde
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potent linear mixed-type inhibitor, competitive with respect to ammonia, no inhibition of the mutant enzyme C379A
guanosine 5'-tetraphosphate
no guanosine, kact: 4/sec, KA: 0.19 mM, Ki: 0.5 mM; the GTP analogue is capable of inhibiting Gln-dependent CTP formation at over 0.15 mM
ITP
no guanosine, kact: 5.2/sec, KA: 2.9 mM, Ki: 4.5 mM; the GTP analogue is capable of inhibiting Gln-dependent CTP formation at over 0.15 mM
L-2-pyrrolidone 5-carboxylate
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weak competitive inhibition of the reaction with ammonia as substrate, no significant inhibition with glutamine as substrate
NH4Cl
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substrate inhibition , a significant part of the inhibition can be shown to be due to the increase in ionic strength with increasing substrate concentrations
Ni2+
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in presence of dithiothreitol inhibition at concentrations below 0.2 mM
O-methylguanosine 5'-triphosphate
no guanosine, kact: 2.8/sec, KA: 0.13 mM, Ki: 0.29 mM
O6-methyl-GTP
the GTP analogue is capable of inhibiting Gln-dependent CTP formation at over 0.15 mM
pyrrole-2-carboxylate
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weak competitive inhibition of the reaction with ammonia as substrate, no significant inhibition with glutamine as substrate
S-nitroso-L-cysteine
specific irreversible inhibitor,inhibits the activity by 94%
S-nitroso-L-homocysteine
specific irreversible inhibitor, inhibits the activity by 90%
Zn2+
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inhibition is reversed by EDTA, in presence of dithiothreitol inhibition at concentrations below 0.2 mM
6-diazo-5-oxo-L-norleucine
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reduces the parasite CTP level even further and inhibits trypanosome proliferation in vitro and in Trypanosoma brucei-infected mice
CTP
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the enzyme from T lymphoblast S49 cells is refractory to complete inhibition by CTP
CTP
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product inhibition of wild-type enzyme, mutant E161K is less sensitive to CTP product inhibition
CTP
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IC50 for the native enzyme: 0.12 in presence of 0.5 mM ATP, 0.22 mM in presence of 1 mM ATP. IC50 for the phosphorylated enzyme: 0.21 mM in presence of 0.5 mM ATP, 0.31 mM in presence of 1 mM ATP
cyclopentenyl cytosine
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the inhibitor has a cytostatic effect on lymphoblasts of children with acute lymphocytic leukemia
cyclopentenyl cytosine
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a highly specific inhibitor of CTPS1, in vivo inhibition leads to alterations in the cell nuclei and microtubule network, overview
GTP
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inhibition of glutamine-dependent CTP formation above 0.15 mM, inhibition of glutamine-dependent CTP formation in a concentration-dependent manner
GTP
0.1 mM guanosine, kact: 10.3/sec, KA: 0.088 mM, Ki: 0.22 mM; 0.2 mM guanosine, kact: 8.2/sec, KA: 0.078 mM, Ki: 0.12 mM; allosteric effector, structural requirements for activation are stringent, but requirements for inhibition are lax. GTP promotes Gln hydrolysis but inhibits Gln-dependent CTP formation at concentrations of over 0.15 mM; no guanosine, kact: 10.6/sec, KA: 0.081 mM, Ki: 0.28 mM
GTP
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GTP acts a positive allosteric effector for Gln-dependent CTP formation. However, at concentrations exceeding 0.15 mM, GTP inhibits Gln-dependent CTP formation. Moreover, GTP is an inhibitor of NH3-dependent CTP formation at all concentrations
GTP
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inhibits glutamine-dependent CTP formation at concentrations above 0.2 mM
additional information
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enzyme loses activity at ionic strengths higher than 0.4 M
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additional information
GTP analogues inhibite NH3-and Gln-dependent CTP-formation, often in a cooperative manner, to a similar extent as they activate it with IC50 values of 0.2-0.5 mM, the inhibition appears to be due solely to the purine base, binding structures and kinetics, overview. Inhibitor structure-activity study, overview
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additional information
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GTP analogues inhibite NH3-and Gln-dependent CTP-formation, often in a cooperative manner, to a similar extent as they activate it with IC50 values of 0.2-0.5 mM, the inhibition appears to be due solely to the purine base, binding structures and kinetics, overview. Inhibitor structure-activity study, overview
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additional information
incubation of EcCTPS modified by CysNO and HcyNO with 5 mM DTT for 30 min at 37°C reveals that 88% and 97%, respectively, of the original activity can be recovered; it is shown that in the presence of 1 mM Gln, S-nitroso-L-cysteine reduces the enzymatic activity by 88% and by 32% in the presence of 10 mM Gln. Similar studies with S-nitroso-L-homocysteine result in reduction of the activity by 43% and 19%, respectively. The results suggest that the substrate Gln competitively protects the active site of EcCTPS from the modification with S-nitroso-L-cysteine and S-nitroso-L-homocysteine.; no inhibition by S-nitrosoglutathione presumably due to its inability to enter the actve site of the enzyme
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additional information
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inhibition by xanthine and derivatives, no inhibition by allantoin, an intact purine ring with anionic character favors inhibition. In general, methylation of the purine does not significantly affect inhibition
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