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6.3.2.17: tetrahydrofolate synthase

This is an abbreviated version!
For detailed information about tetrahydrofolate synthase, go to the full flat file.

Word Map on EC 6.3.2.17

Reaction

ATP
+
tetrahydropteroyl-[gamma-Glu]n
 +
L-glutamate
=
ADP
 +
phosphate
 +
tetrahydropteroyl-[gamma-Glu]n+1

Synonyms

100194131, AtDFB, cFPGS, DHFS/FPGS, dihydrofolate synthase/folylpolyglutamate synthase, eFPGS, Folate polyglutamate synthetase, FolC, folyl-gamma-glutamate synthetase, Folylpoly(.gamma.-glutamate) synthase, Folylpoly-.gamma.-glutamate synthase, Folylpoly-gamma-glutamate synthetase, Folylpoly-gamma-glutamate synthetase-dihydrofolate synthetase, Folylpolyglutamate synthase, Folylpolyglutamate synthetase, folylpolyglutamate synthetase 1, Folylpolyglutamyl synthetase, folypoly-gamma-glutamate synthetase, folypolyformyl glutamate synthase, folypolyglutamate synthase, folypolyglutamate synthetase, Formyltetrahydropteroyldiglutamate synthetase, FPGS, FPGS1, FPGS2, GRMZM2G393334, mFGPS, mFPGS, More, MTHFD1L, N10-Formyltetrahydropteroyldiglutamate synthetase, PfDHFS-FPGS, Synthetase, folylpolyglutamate, Tail length regulator, tetrahydrofolate:L-glutamate gamma-ligase (ADP-forming), tetrahydrofolylpolyglutamate synthase

ECTree

     6 Ligases
         6.3 Forming carbon-nitrogen bonds
             6.3.2 Acid—amino-acid ligases (peptide synthases)
                6.3.2.17 tetrahydrofolate synthase

Inhibitors

Inhibitors on EC 6.3.2.17 - tetrahydrofolate synthase

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INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
(2S)-2-(o-fluoro-p-(N-(2,7-dimethyl-4-oxo-3,4-dihydroquinazolin-6-yl)methyl)-N-(prop-2-ynyl-amino)benzamido)-4-(tetrazol-5-yl)butyric acid
(6R)-10-formyl-5,6,7,8-tetrahydropteroylpentaglutamate
-
-
(6R)-5,10-dideaza-5,6,7,8-tetrahydropteroyl-L-glutamate-gamma-L-glutamate
-
-
(6R)-5,10-dideaza-5,6,7,8-tetrahydropteroyl-L-glutamate-gamma-L-glutamate-gamma-L-glutamate
-
-
(6R)-5,10-dideaza-5,6,7,8-tetrahydropteroyl-L-glutamate-gamma-L-glutamate-gamma-L-glutamate-gamma-L-glutamate
-
-
(6R)-5,10-dideaza-5,6,7,8-tetrahydropteroyl-L-glutamate-gamma-L-glutamate-gamma-L-glutamate-gamma-L-glutamate-gamma-L-glutamate
-
-
(6R)-5,10-dideaza-5,6,7,8-tetrahydropteroyl-L-glutamate-gamma-L-glutamate-gamma-L-glutamate-gamma-L-glutamate-gamma-L-glutamate-gamma-L-glutamate
-
-
(6S)-5,10-dideaza-5,6,7,8-tetrahydrofolate
-
-
(6S)-5,10-dideaza-5,6,7,8-tetrahydropteroyl-L-glutamate-gamma-L-glutamate
-
-
(6S)-5,10-methylene-5,6,7,8-tetrahydropteroylpentaglutamate
-
-
(6S)-5,6,7,8-tetrahydropteroylpentaglutamate
-
-
(6S)-5-formyl-5,6,7,8-tetrahydropteroylpentaglutamate
-
-
(6S)-5-methyl-5,6,7,8-tetrahydropteroylpentaglutamate
-
-
(NH4)2SO4
-
-
(S)-2(5-(((1,2-dihydro-3-methyl-1-oxobenzo-(f)quinazolin-9-yl)methyl)-1-oxo-2-isoindolinyl))-glutaric acid
-
IC50 of 0.0000009 mM in the wild type cell line, IC50 of 0.0000012 mM to 0.000539 mM in the antifolates-resistant sublines
2,4-Diamino-pteroyl-Orn
-
-
2-Amino-4-oxo-5,8-dideazapteroyl-Orn
-
-
2-[[(4-[[(2-amino-4-oxo-3,4-dihydropteridin-6-yl)methyl]amino]phenyl)(hydroxy)phosphoryl]methyl]pentanedioic acid
-
-
2-[[[(3S)-3-[(4-[[(2-amino-4-oxo-3,4-dihydropteridin-6-yl)methyl]amino]benzoyl)amino]-3-carboxypropyl](hydroxy)phosphoryl]methyl]pentanedioic acid
-
-
2-[[[(4S)-4-carboxy-4-[(4-[[(2,4-diaminopteridin-6-yl)methyl](methyl)amino]benzoyl)amino]butyl](hydroxy)phosphoryl]methyl]pentanedioic acid
-
-
2-[[[(4S)-4-[(4-[2-[(6R)-2-amino-4-oxo-3,4,5,6,7,8-hexahydropyrido[2,3-d]pyrimidin-6-yl]ethyl]benzoyl)amino]-4-carboxybutyl](hydroxy)phosphoryl]methyl]pentanedioic acid
-
-
2-[[[(4S)-4-[(4-[[(2-amino-4-oxo-3,4-dihydropteridin-6-yl)methyl]amino]benzoyl)amino]-4-carboxybutyl](hydroxy)phosphoryl]methyl]pentanedioic acid
-
-
3,3-Difluoroglutamic acid
3-(N-phosphonoacetyl)amino-2-L-(N-pteroylamino)propanoic acid
-
slight inhibition at 0.1 mM
3-N-(methoxyphosphono)acetylamino-2-L-(N-pteroylamino)propanoic acid
-
slight inhibition at 0.1 mM
4-amino-4-deoxypteroyl-L-ornithine
-
-
4-threo-Fluoroglutamate
-
prevents or severly retards further addition of Glu
5,10-dideaza-5,6,7,8-tetrahydrofolic acid
5,6,7,8-tetrahydrofolyl-Glu2
-
60% inhibition of ATP binding at 0.1 mM
5,6,7,8-Tetrahydropteroate
-
5,6,7,8-tetrahydropteroyl-Glu2 formation
5,6,7,8-Tetrahydropteroyl-Orn
5-fluorouracil
-
FPGS overexpression significantly enhances chemosensitivity to 5-fluorouracil, FPGS inhibition decreases chemosensitivity to 5-fluorouracil
7,8-dihydropteroate
-
5,6,7,8-tetrahydropteroyl-Glu2 formation
7,8-dihydropteroyl-Glu
-
5,6,7,8-tetrahydropteroyl-Glu2 formation
adenosine 5'-O-(3-thiotriphosphate)
-
-
aminopterin
ATP4-
beta,gamma-Imido-ATP
-
-
beta,gamma-methylene-ATP
dihydrofolate
-
treatment of cells with trimethoprim leads to inhibition due to accumulation of dihydrofolate through the inhibition of dihydrofolate reductase. Therefore falling dihydrofolate reductase activity leads to falling folylpolyglutamate synthase activity in a domino-like cascade
Dihydropteroic acid
-
5% inhibition of ATP binding at 0.1 mM
diphosphate
Endogenous inhibitor from Neurospora crassa
-
Folate analogs
-
-
iodoacetamide
-
2 mM, 30 to 85% loss of activity in 5 min, depending on the enzyme concentration
K+
-
required at low concentration, inhibition at high concentration
L-Glu-gamma-methylester
-
-
L-Homocysteate
methotrexate
methotrexate-Glu
methotrexate-phosphinate
-
competitive inhibition, IC50 of 0.000008 mM, at fixed substrate and recombinant enzyme concentrations. The most potent FPGS inhibitor based on methotrexate heterocycle. CCRF-CEM R2 subline does not respond to inhibition by this compound at 0.001 mM
methotrexate-phosphonate
-
IC50 0.00012 mM, at fixed substrate and recombinant enzyme concentrations
N-(4-(2(2-amino-3,4-dihydro-4-oxo-7H-pyrolo-(2,3-d)pyrimidine-5-yl)ethyl)-benzoyl)-L-glutamic acid
-
IC50 of 0.0000136 mM in the wild type cell line, IC50 of 0.000116 mM in the MTA-13 cell line
N-(4-[[(2-amino-4-oxo-3,4-dihydropteridin-6-yl)methyl]amino]benzoyl)-L-gamma-glutamyl-5-[(2,4-dicarboxybutyl)(hydroxy)phosphoryl]-L-norvaline
-
-
N-(5-(N-(3,4-dihydro-2-methyl-4-oxoquinazolin-6-ylmethyl)-N-methylamino)-2-thenoyl)L-glutamic acid
Nalpha-(4-amino-4-deoxy-5,8-diazapteroyl)-L-ornithine
-
-
Nalpha-(4-amino-4-deoxy-5,chloropteroyl)-L-ornithine
-
-
Nalpha-(4-amino-4-deoxy-8-deazapteroyl)-L-ornithine
-
-
Nalpha-(4-amino-4-deoxy-N10-methylpteroyl)-Nepsilon-(phosphonoacetyl)-L-lysine
-
slight inhibition at 0.1 mM
Nalpha-(4-amino-4-deoxypteroyl)-Ndelta-hemiphthaloyl-L-ornithine
-
IC50 of 0.000001 mM in the wild type cell line, IC50 of 0.000006 mM to 0.0017 mM in the antifolates-resistant sublines
Nalpha-(5,8-dideaza-5-chloropteroyl)-L-ornithine
-
-
Nalpha-(5,8-dideazapteroyl)-L-ornithine
-
-
Nalpha-pteroyl-L-ornithine
-
-
NH4+
-
required at low concentration, inhibition at high concentration
Non-gamma-glutamylatable antifolate analogs
-
aminopterin analogs are better inhibitors than their methotrexate counterparts
-
Ornithine-containing folate analogs
-
e.g. 2,4-diamino-pteroylornithine, 2-amino-4-oxo-5,8-dideazapteroyl-Orn
-
P1,P5-di(adenosine-5')pentaphosphate
-
-
pemetrexed
-
-
pemetrexed disodium
-
ALIMTA, no inhibition observed with the 5,10-dideazatetrahydrofolate resistant cells sublines
phosphate
Rb+
-
required at low concentration, inhibition at high concentration
trimethoprim
-
treatment of cells leads to inhibition due to accumulation of dihydrofolate through the inhibition of dihydrofolate reductase. Therefore falling dihydrofolate reductase activity leads to falling folylpolyglutamate synthase activity in a domino-like cascade
additional information
-