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Literature summary extracted from

  • Lunn, F.A.; Macdonnell, J.E.; Bearne, S.L.
    Structural requirements for the activation of Escherichia coli CTP synthase by the allosteric effector GTP are stringent, but requirements for inhibition are Lax (2007), J. Biol. Chem., 283, 2010-2020.
    View publication on PubMed

Activating Compound

EC Number Activating Compound Comment Organism Structure
6.3.4.2 2'-deoxy-GTP 0 mM guanosine, kact: 1.5/sec, KA: 0.21 mM, Ki: 0.36 mM Escherichia coli
6.3.4.2 2'-deoxy-GTP the GTP analogue is capable of activating Gln-dependent CTP formation Escherichia coli
6.3.4.2 6-thio-GTP the GTP analogue is capable of activating Gln-dependent CTP formation Escherichia coli
6.3.4.2 6-thioguanosine 5'-triphosphate 0 mM guanosine, kact: 8.5/sec, KA: 0.035 mM, Ki: 0.27 mM Escherichia coli
6.3.4.2 GTP 0 mM guanosine, kact: 10.6/sec, KA: 0.081 mM, Ki: 0.28 mM Escherichia coli
6.3.4.2 GTP 0.1 mM guanosine, kact: 10.3/sec, KA: 0.088 mM, Ki: 0.22 mM Escherichia coli
6.3.4.2 GTP 0.2 mM guanosine, kact: 8.2/sec, KA: 0.078 mM, Ki: 0.12 mM Escherichia coli
6.3.4.2 GTP 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 Escherichia coli
6.3.4.2 guanosine 5'-tetraphosphate 0 mM guanosine, kact: 4/sec, KA: 0.19 mM, Ki: 0.5 mM Escherichia coli
6.3.4.2 guanosine 5'-tetraphosphate the GTP analogue is capable of activating Gln-dependent CTP formation Escherichia coli
6.3.4.2 ITP 0 mM guanosine, kact: 5.2/sec, KA: 2.9 mM, Ki: 4.5 mM Escherichia coli
6.3.4.2 ITP the GTP analogue is capable of activating Gln-dependent CTP formation Escherichia coli
6.3.4.2 additional information activation potency in descending order: GTP = 6-thio-GTP, ITP = guanosine 5'-tetraphosphate, O6-methyl-GTP, 2'-deoxy-GTP, no activation with guanosine, GMP, GDP, 2',3'-dideoxy-GTP, acycloguanosine, and acycloguanosine monophosphate, indicating that the 5'-triphosphate, 2'-OH, and 3'-OH are required for full activation, binding structures and kinetics, overview Escherichia coli
6.3.4.2 O-methylguanosine 5'-triphosphate 0 mM guanosine, kact: 2.8/sec, KA: 0.13 mM, Ki: 0.29 mM Escherichia coli
6.3.4.2 O6-methyl-GTP the GTP analogue is capable of activating Gln-dependent CTP formation Escherichia coli

Application

EC Number Application Comment Organism
6.3.4.2 drug development modifying 2-aminopurine or 2-aminopurine riboside may serve as an effective strategy for developing CTPS inhibitors Escherichia coli

Cloned(Commentary)

EC Number Cloned (Comment) Organism
6.3.4.2 cloned in Escherichia coli as a histidine-tagged fusion protein Escherichia coli

Inhibitors

EC Number Inhibitors Comment Organism Structure
6.3.4.2 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 Escherichia coli
6.3.4.2 2'-deoxy-guanosine
-
 Escherichia coli
6.3.4.2 2,6-diaminopurine riboside
-
 Escherichia coli
6.3.4.2 2-aminopurine riboside
-
 Escherichia coli
6.3.4.2 3'-deoxy-guanosine
-
 Escherichia coli
6.3.4.2 6-thio-GTP the GTP analogue is capable of inhibiting Gln-dependent CTP formation at over 0.15 mM Escherichia coli
6.3.4.2 6-thioguanine
-
 Escherichia coli
6.3.4.2 6-thioguanosine
-
 Escherichia coli
6.3.4.2 6-thioguanosine 5'-triphosphate no guanosine, kact: 8.5/sec, KA: 0.035 mM, Ki: 0.27 mM Escherichia coli
6.3.4.2 7-deazaguanosine
-
 Escherichia coli
6.3.4.2 8-oxoguanosine
-
 Escherichia coli
6.3.4.2 8-oxoguanosine 5'-triphosphate
-
 Escherichia coli
6.3.4.2 acycloguanosine
-
 Escherichia coli
6.3.4.2 acycloguanosine monophosphate
-
 Escherichia coli
6.3.4.2 adenosine
-
 Escherichia coli
6.3.4.2 dideoxy-GTP
-
 Escherichia coli
6.3.4.2 GDP
-
 Escherichia coli
6.3.4.2 GMP
-
 Escherichia coli
6.3.4.2 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 Escherichia coli
6.3.4.2 guanosine
-
 Escherichia coli
6.3.4.2 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 Escherichia coli
6.3.4.2 Inosine
-
 Escherichia coli
6.3.4.2 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 Escherichia coli
6.3.4.2 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 Escherichia coli
6.3.4.2 N-methylguanosine
-
 Escherichia coli
6.3.4.2 O-methylguanosine
-
 Escherichia coli
6.3.4.2 O-methylguanosine 5'-triphosphate no guanosine, kact: 2.8/sec, KA: 0.13 mM, Ki: 0.29 mM Escherichia coli
6.3.4.2 O6-methyl-GTP the GTP analogue is capable of inhibiting Gln-dependent CTP formation at over 0.15 mM Escherichia coli
6.3.4.2 Xanthosine
-
 Escherichia coli

KM Value [mM]

EC Number KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
6.3.4.2 additional information
-
 additional information kinetic mechanism, activation and inhibition kinetics Escherichia coli

Metals/Ions

EC Number Metals/Ions Comment Organism Structure
6.3.4.2 Mg2+
-
 Escherichia coli
6.3.4.2 Mg2+ assay with 10 mM MgCl2 Escherichia coli

Natural Substrates/ Products (Substrates)

EC Number Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
6.3.4.2 ATP + UTP + L-glutamine Escherichia coli
-
 ADP + phosphate + CTP + L-glutamate
-
 ?
6.3.4.2 ATP + UTP + NH3 Escherichia coli
-
 ADP + phosphate + CTP
-
 ?

Organism

EC Number Organism UniProt Comment Textmining
6.3.4.2 Escherichia coli P0A7E5
-
-

Purification (Commentary)

EC Number Purification (Comment) Organism
6.3.4.2 the soluble histidine-tagged CTPS is purified using metal ion affinity chromatography and the histidine tag is subsequently removed using thrombin-catalyzed cleavage Escherichia coli

Specific Activity [micromol/min/mg]

EC Number Specific Activity Minimum [µmol/min/mg] Specific Activity Maximum [µmol/min/mg] Comment Organism
6.3.4.2 additional information
-
 a structure-activity study using a variety of GTP and guanosine analogues reveals that only a few GTP analogues are capable of activating Gln-dependent CTP formation to varying degrees: GTP > 6-thio-GTP > ITP> guanosine 5'-tetraphosphate > O-methyl-GTP > 2'-deoxy-GTP. No activation is observed with guanosine, GMP, GDP, 2',3'-dideoxy-GTP, acycloguanosine, and acycloguanosine monophosphate indicating that the 5'-triphosphate, 2'-OH, and 3'-OH are required for full activation. The 2-NH2 group is important in binding recognition while substituents at the 6-position are important in activation. Escherichia coli

Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
6.3.4.2 ATP + UTP + Gln + H2O
-
 Escherichia coli ADP + CTP + Glu + phosphate
-
 ?
6.3.4.2 ATP + UTP + L-glutamine
-
 Escherichia coli ADP + phosphate + CTP + L-glutamate
-
 ?
6.3.4.2 ATP + UTP + NH3
-
 Escherichia coli ADP + CTP + phosphate
-
 ?
6.3.4.2 ATP + UTP + NH3
-
 Escherichia coli ADP + phosphate + CTP
-
 ?
6.3.4.2 deoxyGTP + UTP + NH4+
-
 Escherichia coli deoxyGDP + phosphate + CTP
-
 ?
6.3.4.2 GTP + UTP + NH4+
-
 Escherichia coli GDP + phosphate + CTP
-
 ?

Synonyms

EC Number Synonyms Comment Organism
6.3.4.2 CTP synthase
-
 Escherichia coli
6.3.4.2 CTPS
-
 Escherichia coli
6.3.4.2 cytidine 5'-triphosphate synthase
-
 Escherichia coli
6.3.4.2 UTP:ammonia ligase (ADP-forming)
-
 Escherichia coli

Temperature Optimum [°C]

EC Number Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
6.3.4.2 37
-
 assay at Escherichia coli

Turnover Number [1/s]

EC Number Turnover Number Minimum [1/s] Turnover Number Maximum [1/s] Substrate Comment Organism Structure
6.3.4.2 1.5
-
 2'-deoxy-GTP no guanosine Escherichia coli
6.3.4.2 2.8
-
 O-methylguanosine 5'-triphosphate no guanosine Escherichia coli
6.3.4.2 4
-
 guanosine 5'-tetraphosphate no guanosine Escherichia coli
6.3.4.2 5.2
-
 ITP no guanosine Escherichia coli
6.3.4.2 8.2
-
 GTP 0.2 mM guanosine Escherichia coli
6.3.4.2 8.5
-
 6-thioguanosine 5'-triphosphate no guanosine, kact: 8.5/sec, KA: 0.035 mM, Ki: 0.27 mM Escherichia coli
6.3.4.2 10.3
-
 GTP 0.1 mM guanosine Escherichia coli
6.3.4.2 10.6
-
 GTP no guanosine Escherichia coli

pH Optimum

EC Number pH Optimum Minimum pH Optimum Maximum Comment Organism
6.3.4.2 8
-
 assay at Escherichia coli

Cofactor

EC Number Cofactor Comment Organism Structure
6.3.4.2 ATP dependent on Escherichia coli

Ki Value [mM]

EC Number Ki Value [mM] Ki Value maximum [mM] Inhibitor Comment Organism Structure
6.3.4.2 additional information
-
 additional information nucleotide and nucleoside analogues of GTP and guanosine, respectively, all inhibit NH3- and Gln-dependent CTP formation to a similar extent (IC50 : 0.2–0.5 mM). This inhibition appears to be due solely to the purine base and is relatively insensitive to the identity of the purine with the exception of inosine, ITP, and adenosine (IC50 : 4–12 mM). 8-Oxoguanosine is the best inhibitor identified (IC50 : 0.08 mM). Escherichia coli
6.3.4.2 additional information
-
 additional information kinetic mechanism, activation and inhibition kinetics Escherichia coli
6.3.4.2 0.12
-
 GTP 0.2 mM guanosine Escherichia coli
6.3.4.2 0.22
-
 GTP 0.1 mM guanosine Escherichia coli
6.3.4.2 0.27
-
 6-thioguanosine 5'-triphosphate
-
 Escherichia coli
6.3.4.2 0.28
-
 GTP no guanosine Escherichia coli
6.3.4.2 0.29
-
 O-methylguanosine 5'-triphosphate
-
 Escherichia coli
6.3.4.2 0.36
-
 2'-deoxy-GTP
-
 Escherichia coli
6.3.4.2 0.5
-
 guanosine 5'-tetraphosphate
-
 Escherichia coli
6.3.4.2 4.5
-
 ITP
-
 Escherichia coli

IC50 Value

EC Number IC50 Value IC50 Value Maximum Comment Organism Inhibitor Structure
6.3.4.2 0.08
-
-
 Escherichia coli 8-oxoguanosine
6.3.4.2 0.08
-
 IC50 for inhibition of Gln-dependent CTP formation Escherichia coli 8-oxoguanosine
6.3.4.2 0.11
-
 IC50 for inhibition of Gln-dependent CTP formation Escherichia coli 2,6-diaminopurine riboside
6.3.4.2 0.11
-
 IC50 for inhibition of Gln-dependent CTP formation Escherichia coli 8-oxoguanosine 5'-triphosphate
6.3.4.2 0.13
-
 IC50 for inhibition of NH3-dependent CTP formation Escherichia coli 8-oxoguanosine
6.3.4.2 0.15
-
 0.30 mM Gln, IC50 for inhibition of Gln-dependent CTP formation Escherichia coli O-methylguanosine
6.3.4.2 0.15
-
 IC50 for inhibition of NH3-dependent CTP formation Escherichia coli 8-oxoguanosine 5'-triphosphate
6.3.4.2 0.16
-
 10 mM Gln, IC50 for inhibition of Gln-dependent CTP formation Escherichia coli O-methylguanosine
6.3.4.2 0.16
-
 2.5 mM Gln, IC50 for inhibition of Gln-dependent CTP formation Escherichia coli O-methylguanosine
6.3.4.2 0.16
-
 IC50 for inhibition of Gln-dependent CTP formation Escherichia coli O-methylguanosine
6.3.4.2 0.17
-
 0.75 mM Gln, IC50 for inhibition of Gln-dependent CTP formation Escherichia coli O-methylguanosine
6.3.4.2 0.17
-
 IC50 for inhibition of Gln-dependent CTP formation Escherichia coli N-methylguanosine
6.3.4.2 0.18
-
 IC50 for inhibition of NH3-dependent CTP formation Escherichia coli 2,6-diaminopurine riboside
6.3.4.2 0.22
-
 5.44 mM NH3, IC50 for inhibition of NH3-dependent CTP formation Escherichia coli guanosine
6.3.4.2 0.22
-
 IC50 for inhibition of Gln-dependent CTP formation Escherichia coli Xanthosine
6.3.4.2 0.22
-
 IC50 for inhibition of Gln-dependent CTP formation Escherichia coli 2-aminopurine riboside
6.3.4.2 0.23
-
 5.44 mM NH3, IC50 for inhibition of NH3-dependent CTP formation Escherichia coli GMP
6.3.4.2 0.23
-
 IC50 for inhibition of Gln-dependent CTP formation Escherichia coli 6-thioguanosine
6.3.4.2 0.23
-
 IC50 for inhibition of NH3-dependent CTP formation Escherichia coli N-methylguanosine
6.3.4.2 0.25
-
 2.72 mM NH3, IC50 for inhibition of NH3-dependent CTP formation Escherichia coli GMP
6.3.4.2 0.25
-
 IC50 for inhibition of NH3-dependent CTP formation Escherichia coli O-methylguanosine
6.3.4.2 0.26
-
 1.36 mM NH3, IC50 for inhibition of NH3-dependent CTP formation Escherichia coli guanosine
6.3.4.2 0.26
-
 2.72 mM NH3, IC50 for inhibition of NH3-dependent CTP formation Escherichia coli guanosine
6.3.4.2 0.26
-
 IC50 for inhibition of NH3-dependent CTP formation Escherichia coli GMP
6.3.4.2 0.26
-
 IC50 for inhibition of NH3-dependent CTP formation Escherichia coli 2-aminopurine riboside
6.3.4.2 0.28
-
 1.36 mM NH3, IC50 for inhibition of NH3-dependent CTP formation Escherichia coli GMP
6.3.4.2 0.29
-
 2.72 mM NH3, IC50 for inhibition of NH3-dependent CTP formation Escherichia coli GDP
6.3.4.2 0.29
-
 5.44 mM NH3, IC50 for inhibition of NH3-dependent CTP formation Escherichia coli GTP
6.3.4.2 0.29
-
 5.44 mM NH3, IC50 for inhibition of NH3-dependent CTP formation Escherichia coli GDP
6.3.4.2 0.29
-
 8.16 mM NH3, IC50 for inhibition of NH3-dependent CTP formation Escherichia coli GMP
6.3.4.2 0.29
-
 8.16 mM NH3, IC50 for inhibition of NH3-dependent CTP formation Escherichia coli guanosine
6.3.4.2 0.29
-
 IC50 for inhibition of Gln-dependent CTP formation Escherichia coli dideoxy-GTP
6.3.4.2 0.29
-
 IC50 for inhibition of NH3-dependent CTP formation Escherichia coli GDP
6.3.4.2 0.29
-
 IC50 for inhibition of NH3-dependent CTP formation Escherichia coli guanosine
6.3.4.2 0.29
-
 IC50 for inhibition of NH3-dependent CTP formation Escherichia coli Xanthosine
6.3.4.2 0.3
-
 0.30 mM Gln, IC50 for inhibition of Gln-dependent CTP formation Escherichia coli guanosine
6.3.4.2 0.3
-
 1.36 mM NH3, IC50 for inhibition of NH3-dependent CTP formation Escherichia coli GDP
6.3.4.2 0.3
-
 2.72 mM NH3, IC50 for inhibition of NH3-dependent CTP formation Escherichia coli GTP
6.3.4.2 0.3
-
 8.16 mM NH3, IC50 for inhibition of NH3-dependent CTP formation Escherichia coli GTP
6.3.4.2 0.3
-
 IC50 for inhibition of NH3-dependent CTP formation Escherichia coli GTP
6.3.4.2 0.31
-
 1.36 mM NH3, IC50 for inhibition of NH3-dependent CTP formation Escherichia coli GTP
6.3.4.2 0.31
-
 IC50 for inhibition of Gln-dependent CTP formation Escherichia coli acycloguanosine monophosphate
6.3.4.2 0.32
-
 10 mM Gln, IC50 for inhibition of Gln-dependent CTP formation Escherichia coli guanosine
6.3.4.2 0.32
-
 2.5 mM Gln, IC50 for inhibition of Gln-dependent CTP formation Escherichia coli guanosine
6.3.4.2 0.32
-
 IC50 for inhibition of Gln-dependent CTP formation Escherichia coli guanosine
6.3.4.2 0.33
-
 IC50 for inhibition of Gln-dependent CTP formation Escherichia coli GDP
6.3.4.2 0.33
-
 IC50 for inhibition of Gln-dependent CTP formation Escherichia coli GMP
6.3.4.2 0.33
-
 IC50 for inhibition of Gln-dependent CTP formation Escherichia coli guanosine 5'-tetraphosphate
6.3.4.2 0.33
-
 IC50 for inhibition of Gln-dependent CTP formation Escherichia coli acycloguanosine
6.3.4.2 0.33
-
 IC50 for inhibition of Gln-dependent CTP formation Escherichia coli 2'-deoxy-GTP
6.3.4.2 0.33
-
 IC50 for inhibition of Gln-dependent CTP formation Escherichia coli 2'-deoxy-guanosine
6.3.4.2 0.34
-
 IC50 for inhibition of Gln-dependent CTP formation Escherichia coli 3'-deoxy-guanosine
6.3.4.2 0.35
-
 0.75 mM Gln, IC50 for inhibition of Gln-dependent CTP formation Escherichia coli guanosine
6.3.4.2 0.39
-
 IC50 for inhibition of Gln-dependent CTP formation Escherichia coli 6-thioguanine
6.3.4.2 0.4
-
 IC50 for inhibition of NH3-dependent CTP formation Escherichia coli 6-thioguanosine
6.3.4.2 0.4
-
 IC50 for inhibition of NH3-dependent CTP formation Escherichia coli 3'-deoxy-guanosine
6.3.4.2 0.41
-
 IC50 for inhibition of NH3-dependent CTP formation Escherichia coli dideoxy-GTP
6.3.4.2 0.41
-
 IC50 for inhibition of NH3-dependent CTP formation Escherichia coli acycloguanosine monophosphate
6.3.4.2 0.42
-
 IC50 for inhibition of NH3-dependent CTP formation Escherichia coli guanosine 5'-tetraphosphate
6.3.4.2 0.42
-
 IC50 for inhibition of NH3-dependent CTP formation Escherichia coli 2'-deoxy-GTP
6.3.4.2 0.45
-
 8.16 mM NH3, IC50 for inhibition of NH3-dependent CTP formation Escherichia coli acycloguanosine
6.3.4.2 0.45
-
 IC50 for inhibition of NH3-dependent CTP formation Escherichia coli acycloguanosine
6.3.4.2 0.45
-
 IC50 for inhibition of NH3-dependent CTP formation Escherichia coli 2'-deoxy-guanosine
6.3.4.2 0.47
-
 5.44 mM NH3, IC50 for inhibition of NH3-dependent CTP formation Escherichia coli acycloguanosine
6.3.4.2 0.48
-
 2.72 mM NH3, IC50 for inhibition of NH3-dependent CTP formation Escherichia coli acycloguanosine
6.3.4.2 0.49
-
 1.36 mM NH3, IC50 for inhibition of NH3-dependent CTP formation Escherichia coli acycloguanosine
6.3.4.2 0.61
-
 IC50 for inhibition of NH3-dependent CTP formation Escherichia coli 6-thioguanine
6.3.4.2 2.9
-
 8.16 mM NH3, IC50 for inhibition of NH3-dependent CTP formation Escherichia coli ITP
6.3.4.2 3
-
 2.72 mM NH3, IC50 for inhibition of NH3-dependent CTP formation Escherichia coli ITP
6.3.4.2 3.1
-
 5.44 mM NH3, IC50 for inhibition of NH3-dependent CTP formation Escherichia coli ITP
6.3.4.2 3.3
-
 1.36 mM NH3, IC50 for inhibition of NH3-dependent CTP formation Escherichia coli ITP
6.3.4.2 3.5
-
 IC50 for inhibition of NH3-dependent CTP formation Escherichia coli Inosine
6.3.4.2 3.7
-
 IC50 for inhibition of NH3-dependent CTP formation Escherichia coli ITP
6.3.4.2 4.1
-
 IC50 for inhibition of Gln-dependent CTP formation Escherichia coli ITP
6.3.4.2 5.2
-
 IC50 for inhibition of Gln-dependent CTP formation Escherichia coli Inosine
6.3.4.2 11
-
 IC50 for inhibition of Gln-dependent CTP formation Escherichia coli adenosine
6.3.4.2 12
-
 IC50 for inhibition of NH3-dependent CTP formation Escherichia coli adenosine