Information on EC 6.3.2.17 - tetrahydrofolate synthase

New: Word Map on EC 6.3.2.17
Please wait a moment until all data is loaded. This message will disappear when all data is loaded.
Specify your search results
Mark a special word or phrase in this record:
Search Reference ID:
Select one or more organisms in this record:
Show additional data
Do not include text mining results
Include (text mining) results (more...)
Include results (AMENDA + additional results, but less precise; more...)


The expected taxonomic range for this enzyme is: Eukaryota, Bacteria

EC NUMBER
COMMENTARY hide
6.3.2.17
-
RECOMMENDED NAME
GeneOntology No.
tetrahydrofolate synthase
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
ATP + tetrahydropteroyl-[gamma-Glu]n + L-glutamate = ADP + phosphate + tetrahydropteroyl-[gamma-Glu]n+1
show the reaction diagram
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
carboxamide formation
-
-
-
-
carboxylic acid amide formation
-
-
-
-
PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
Folate biosynthesis
-
-
folate polyglutamylation
Metabolic pathways
-
-
SYSTEMATIC NAME
IUBMB Comments
tetrahydropteroyl-gamma-polyglutamate:L-glutamate gamma-ligase (ADP-forming)
In some bacteria, a single protein catalyses both this activity and that of EC 6.3.2.12, dihydrofolate synthase [3], the combined activity of which leads to the formation of the coenzyme polyglutamated tetrahydropteroate (H4PteGlun), i.e. various tetrahydrofolates (H4folate). In contrast, the activities are located on separate proteins in most eukaryotes studied to date [4]. In Arabidopsis thaliana, this enzyme is present as distinct isoforms in the mitochondria, the cytosol and the chloroplast. Each isoform is encoded by a separate gene, a situation that is unique among eukaryotes [4]. As the affinity of folate-dependent enzymes increases markedly with the number of glutamic residues, the tetrahydropteroyl polyglutamates are the preferred coenzymes of C1 metabolism. (reviewed in [5]). The enzymes from different sources (particularly eukaryotes versus prokaryotes) have different substrate specificities with regard to one-carbon substituents and the number of glutamate residues present on the tetrahydrofolates.
CAS REGISTRY NUMBER
COMMENTARY hide
63363-84-8
-
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
-
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
malfunction
metabolism
-
metabolizes methotrexate, a universal component of acute lymphoblastic leukemia, into long-chain poylglutamates, resulting in enhanced cytotoxicity from prolonged inhibition of dihydrofolate reductase and thymidylate synthetase
physiological function
the mitochondrial folylpolyglutamate synthetase catalyzes the conjugation of glutamate residues to the tetrahydrofolate during folate synthesis; the mitochondrial folylpolyglutamate synthetase catalyzes the conjugation of glutamate residues to the tetrahydrofolate during folate synthesis
additional information
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
ATP + (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 + L-glutamate
ADP + (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)butanoyl-Glu + phosphate
show the reaction diagram
-
-
-
?
ATP + (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 + L-glutamate
ADP + (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)butanoyl-L-Glu + phosphate
show the reaction diagram
-
-
-
?
ATP + (6R)-10-formyl-5,6,7,8-tetrahydropteroylglutamate + L-glutamate
ADP + phosphate + (6R)-10-formyl-5,6,7,8-tetrahydropteroyl-Glu2
show the reaction diagram
-
-
-
?
ATP + (6R,S)-5,6,7,8-tetrahydrofolic acid + L-glutamate
ADP + phosphate + (6S)-5,6,7,8-tetrahydrofolyl-gamma-Glu
show the reaction diagram
-
-
-
-
ir
ATP + (6RS)-5,6,7,8-tetrahydrofolic acid + L-glutamate
ADP + phosphate + (6S)-5,6,7,8-tetrahydrofolyl-Glu
show the reaction diagram
ATP + (6RS)-5-methyl-H4-homofolate + Glu
ADP + phosphate + homofolyl-Glun
show the reaction diagram
-
-
-
-
-
ATP + (6S)-5,6,7,8-tetrahydropteroylglutamate + L-glutamate
ADP + phosphate + (6S)-5,6,7,8-tetrahydropteroyl-Glu2
show the reaction diagram
ATP + (6S)-5-formyl-5,6,7,8-tetrahydropteroylglutamate + L-glutamate
ADP + phosphate + (6S)-5-formyl-5,6,7,8-tetrahydropteroyl-Glu2
show the reaction diagram
-
poor substrate
-
?
ATP + (6S)-5-methyl-5,6,7,8-tetrahydropteroylglutamate + L-glutamate
ADP + phosphate + (6S)-5-methyl-5,6,7,8-tetrahydropteroyl-Glu2
show the reaction diagram
-
poor substrate
-
?
ATP + (S)-2(5-(((1,2-dihydro-3-methyl-1-oxobenzo-(f)quinazolin-9-yl)methyl)-1-oxo-2-isoindolinyl))glutaric acid + L-glutamate
ADP + (S)-2(5-(((1,2-dihydro-3-methyl-1-oxobenzo-(f)quinazolin-9-yl)methyl)-1-oxo-2-isoindolinyl))glutaryl-L-Glu + phosphate
show the reaction diagram
-
-
-
?
ATP + 10-formyl-5,6,7,8-tetrahydropteroyl-Glu + Glu
ADP + phosphate + 10-formyl-5,6,7,8-tetrahydropteroyl-gamma-Glu
show the reaction diagram
-
-
-
-
?
ATP + 10-formyl-5,6,7,8-tetrahydropteroyl-Glu + Glu
ADP + phosphate + 10-formyl-5,6,7,8-tetrahydropteroyl-Glu
show the reaction diagram
ATP + 10-formyl-5,6,7,8-tetrahydropteroylglutamate + L-glutamate
ADP + phosphate + 10-formyl-5,6,7,8-tetrahydropteroyl-Glu2
show the reaction diagram
-
-
-
?
ATP + 3,5-difluoromethotrexate + Glu
ADP + phosphate + 3,5-difluoromethotrexyl-Glu
show the reaction diagram
ATP + 3,5-difluoropteroyl-Glu + Glu
ADP + phosphate + 3,5-difluoropteroyl-Glu2
show the reaction diagram
ATP + 3-(N-phosphonoacetyl)amino-2-L-(N-pteroylamino)propanoic acid + L-glutamate
ADP + 3-(N-phosphonoacetyl)amino-2-L-(N-pteroylamino)propanoyl-Glu + phosphate
show the reaction diagram
-
much less effective than folic acid
-
?
ATP + 3-N-(methoxyphosphono)acetylamino-2-L-(N-pteroylamino)propanoic acid + L-glutamate
ADP + 3-N-(methoxyphosphono)acetylamino-2-L-(N-pteroylamino)propanoyl-Glu + phosphate
show the reaction diagram
-
much less effective than folic acid
-
?
ATP + 4-amino-4-deoxypteroyl-L-ornithine + L-glutamate
?
show the reaction diagram
-
-
-
?
ATP + 5,10-dideaza-5,6,7,8-tetrahydrofolic acid + L-glutamate
ADP + 5,10-dideaza-5,6,7,8-tetrahydrofolyl-L-Glu + phosphate
show the reaction diagram
ATP + 5,10-dideazatetrahydrofolic acid + L-glutamate
ADP + 5,10-dideazatetrahydrofolyl-L-Glu + phosphate
show the reaction diagram
ATP + 5,10-methylene-5,6,7,8-tetrahydrofolate-Glu2 + L-glutamate
ADP + phosphate + 5,10-methylene-5,6,7,8-tetrahydrofolyl-Glu3
show the reaction diagram
-
-
-
?
ATP + 5,10-methylene-5,6,7,8-tetrahydrofolic acid + L-Glu
ADP + phosphate + 5,10-methylene-5,6,7,8-tetrahydrofolyl-L-Glu
show the reaction diagram
-
-
-
?
ATP + 5,10-methylene-5,6,7,8-tetrahydrofolic acid + L-glutamate
ADP + phosphate + 5,10-methylene-5,6,7,8-tetrahydrofolyl-Glu
show the reaction diagram
ATP + 5,10-methylene-5,6,7,8-tetrahydropteroyl-gamma-Glun + Glu
ADP + phosphate + 5,10-methylene-5,6,7,8-tetrahydropteroyl-gamma-Glun+1
show the reaction diagram
ATP + 5,10-methylene-tetrahydrofolate-Glu2 + L-glutamate
ADP + phosphate + 5,10-methylene-tetrahydrofolyl-Glu3
show the reaction diagram
-
-
-
?
ATP + 5,6,7,8-tetrahydrofolate-Glu2 + L-glutamate
ADP + phosphate + 5,6,7,8-tetrahydrofolyl-Glu3
show the reaction diagram
ATP + 5,6,7,8-tetrahydrofolic acid + L-Glu
ADP + phosphate + 5,6,7,8-tetrahydrofolyl-Glu
show the reaction diagram
-
-
-
?
ATP + 5,6,7,8-tetrahydrofolic acid + L-glutamate
ADP + phosphate + 5,6,7,8-tetrahydrofolyl-Glu
show the reaction diagram
ATP + 5,6,7,8-tetrahydrofolyl-gamma-(L-Glu)2 + L-Glu
ADP + phosphate + 5,6,7,8-tetrahydrofolyl-gamma-(L-Glu)3
show the reaction diagram
-
-
-
?
ATP + 5,6,7,8-tetrahydropteroate + Glu
ADP + phosphate + 5,6,7,8-terahydropteroyl-Glu
show the reaction diagram
ATP + 5,6,7,8-tetrahydropteroyl-4-aminobutanoyl-Glu + Glu
ADP + phosphate + 5,6,7,8-tetrahydropteroyl-4-aminobutanoyl-Glun
show the reaction diagram
ATP + 5,6,7,8-tetrahydropteroyl-gamma-Glu + Glu
ADP + phosphate + 5,6,7,8-tetrahydropteroyl-gamma-Glu2
show the reaction diagram
ATP + 5,6,7,8-tetrahydropteroyl-Glun + Glu
ADP + phosphate + 5,6,7,8-tetrahydropteroyl-gamma-Glun+1
show the reaction diagram
ATP + 5,6,7,8-tetrahydropteroyl-Gly-Glu + Glu
ADP + phosphate + 5,6,7,8-tetrahydropteroyl-Gly-Glu2
show the reaction diagram
ATP + 5-formyl-5,6,7,8-tetrahydrofolate + L-glutamate
ADP + 5-formyl-5,6,7,8-tetrahydrofolyl-L-Glu + phosphate
show the reaction diagram
-
-
-
?
ATP + 5-formyl-5,6,7,8-tetrahydropteroyl-gamma-Glun + Glu
ADP + phosphate + 5-formyl-5,6,7,8-tetrahydropteroyl-gamma-Glu2
show the reaction diagram
ATP + 5-formyl-5,6,7,8-tetrahydropteroylglutamate + L-glutamate
ADP + phosphate + 5-formyl-5,6,7,8-tetrahydropteroyl-Glu2
show the reaction diagram
-
-
-
?
ATP + 5-methyl-5,6,7,8-tetrahydropteroyl-gamma-Glun + Glu
ADP + phosphate + 5-methyl-5,6,7,8-tetrahydropteroyl-gamma-Glun+1
show the reaction diagram
ATP + 5-methyl-5,6,7,8-tetrahydropteroylglutamate + L-glutamate
ADP + phosphate + 5-methyl-5,6,7,8-tetrahydropteroyl-Glu2
show the reaction diagram
ATP + 6-R 5,10-dideaza-5,6,7,8-tetrahydrofolate-Glu2 + L-glutamate
ADP + phosphate + 5,10-methylene-5,6,7,8-tetrahydrofolyl-Glu3
show the reaction diagram
-
at similar rate as that seen with aminopterin as substrate, endogenous enzyme isolated from liver. More efficient than aminopterin, recombinant liver enzyme
-
?
ATP + 6-S 5,10-dideaza-5,6,7,8-tetrahydrofolate-Glu2 + L-glutamate
ADP + phosphate + 5,10-methylene-5,6,7,8-tetrahydrofolyl-Glu3
show the reaction diagram
-
more efficient than aminopterin, recombinant liver enzyme
-
?
ATP + 7,8-dihydropteroate + Glu
ADP + phosphate + 7,8-dihydropteroyl-Glu
show the reaction diagram
ATP + 7,8-dihydropteroate + L-Glu
ADP + phosphate + 7,8-dihydropteroyl-L-Glu
show the reaction diagram
-
-
-
?
ATP + 7,8-dihydropteroyl-(4-aminobutanoyl)-Glu + Glu
ADP + phosphate + 7,8-dihydropteroyl-(4-aminobutanoyl)-Glu2
show the reaction diagram
-
-
-
-
-
ATP + 7,8-dihydropteroyl-(5-aminovaleryl)-Glu + Glu
ADP + phosphate + 7,8-dihydropteroyl-(5-aminovaleryl)-Glu2
show the reaction diagram
-
-
-
-
-
ATP + 7,8-dihydropteroyl-4-aminobutanoyl-Glu + Glu
ADP + phosphate + 7,8-dihydropteroyl-4-aminobutanoyl-Glun
show the reaction diagram
-
-
n: 3-5
-
ATP + 7,8-dihydropteroyl-beta-Ala-Glu + Glu
ADP + phosphate + 7,8-dihydropteroyl-beta-Ala-Glu2
show the reaction diagram
-
-
-
-
-
ATP + 7,8-dihydropteroyl-Glun + Glu
ADP + phosphate + 7,8-dihydropteroyl-Glun+1
show the reaction diagram
ATP + 7-hydroxymethotrexate + Glu
ADP + phosphate + 7-hydroxymethotrexyl-Glu
show the reaction diagram
-
-
-
-
-
ATP + 9-methyl-pteroylmonoglutamyl + Glu
ADP + phosphate + 9-methyl-pteroylmonoglutamyl-Glu
show the reaction diagram
-
-
-
-
ATP + aminopterin + Glu
ADP + phosphate + aminopteryl-Glu
show the reaction diagram
ATP + aminopterin + L-glutamate
?
show the reaction diagram
ATP + dichloromethotrexate + Glu
ADP + phosphate + dichloromethotrexyl-Glu
show the reaction diagram
-
-
-
-
-
ATP + dihydroaminopterin + Glu
ADP + phosphate + dihydroaminopteryl-Glu
show the reaction diagram
ATP + dihydropteroic acid + L-glutamate
ADP + dihydropteroyl-Glu
show the reaction diagram
-
enhancement of ATP binding is observed in the presence of this substrate. The substrate causes a conformational change in the inactive fraction of the enzyme which allows it to bind ATP
-
?
ATP + homofolate + Glu
ADP + phosphate + L-homocysteyl-Glu
show the reaction diagram
-
-
-
-
-
ATP + L-glutamate + (6R)-5,10-dideaza-5,6,7,8-tetrahydrofolate
ADP + phosphate + (6R)-5,10-dideaza-5,6,7,8-tetrahydropteroyl-L-glutamate-gamma-L-glutamate
show the reaction diagram
-
-
-
-
?
ATP + L-glutamate + (6R)-5,10-dideaza-5,6,7,8-tetrahydropteroyl-L-glutamate-gamma-L-glutamate
ADP + phosphate + (6R)-5,10-dideaza-5,6,7,8-tetrahydropteroyl-L-glutamate-gamma-L-glutamate-gamma-L-glutamate
show the reaction diagram
-
-
-
-
?
ATP + L-glutamate + (6R)-5,10-dideaza-5,6,7,8-tetrahydropteroyl-L-glutamate-gamma-L-glutamate-gamma-L-glutamate
ADP + phosphate + (6R)-5,10-dideaza-5,6,7,8-tetrahydropteroyl-L-glutamate-gamma-L-glutamate-gamma-L-glutamate-gamma-L-glutamate
show the reaction diagram
-
-
-
-
?
ATP + L-glutamate + (6R)-5,10-dideaza-5,6,7,8-tetrahydropteroyl-L-glutamate-gamma-L-glutamate-gamma-L-glutamate-gamma-L-glutamate
ADP + phosphate + (6R)-5,10-dideaza-5,6,7,8-tetrahydropteroyl-L-glutamate-gamma-L-glutamate-gamma-L-glutamate-gamma-L-glutamate-gamma-L-glutamate
show the reaction diagram
-
-
-
-
?
ATP + 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
ADP + phosphate + (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
show the reaction diagram
-
-
-
-
?
ATP + 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
ADP + phosphate + (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-gamma-L-glutamate
show the reaction diagram
-
-
-
-
?
ATP + L-glutamate + (6S)-5,10-dideaza-5,6,7,8-tetrahydrofolate
ADP + phosphate + (6S)-5,10-dideaza-5,6,7,8-tetrahydropteroyl-L-glutamate-gamma-L-glutamate
show the reaction diagram
-
-
-
-
?
ATP + L-glutamate + (6S)-5,10-dideaza-5,6,7,8-tetrahydropteroyl-L-glutamate-gamma-L-glutamate
ADP + phosphate + (6S)-5,10-dideaza-5,6,7,8-tetrahydropteroyl-L-glutamate-gamma-L-glutamate-gamma-L-glutamate
show the reaction diagram
-
-
-
-
?
ATP + L-glutamate + (6S)-5,10-dideaza-5,6,7,8-tetrahydropteroyl-L-glutamate-gamma-L-glutamate-gamma-L-glutamate
ADP + phosphate + (6S)-5,10-dideaza-5,6,7,8-tetrahydropteroyl-L-glutamate-gamma-L-glutamate-gamma-L-glutamate-gamma-L-glutamate
show the reaction diagram
-
-
-
-
?
ATP + L-glutamate + (6S)-5,10-dideaza-5,6,7,8-tetrahydropteroyl-L-glutamate-gamma-L-glutamate-gamma-L-glutamate-gamma-L-glutamate
ADP + phosphate + (6S)-5,10-dideaza-5,6,7,8-tetrahydropteroyl-L-glutamate-gamma-L-glutamate-gamma-L-glutamate-gamma-L-glutamate-gamma-L-glutamate
show the reaction diagram
-
-
-
-
?
ATP + L-glutamate + (6S)-5,10-dideaza-5,6,7,8-tetrahydropteroyl-L-glutamate-gamma-L-glutamate-gamma-L-glutamate-gamma-L-glutamate-gamma-L-glutamate
ADP + phosphate + (6S)-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
show the reaction diagram
-
-
-
-
?
ATP + L-glutamate + (6S)-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
ADP + phosphate + (6S)-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-gamma-L-glutamate
show the reaction diagram
-
-
-
-
?
ATP + L-glutamate + tetrahydrofolate-Glu
ADP + phosphate + tetrahydrofolyl-Glu2
show the reaction diagram
-
assay at pH 10, 37C
-
-
?
ATP + L-homocysteate + Glu
ADP + phosphate + (6RS)-5-methyl-H4-homofolyl-Glu
show the reaction diagram
-
-
-
-
-
ATP + methotrexate + 3,3-difluoroglutamate
ADP + phosphate + methotrexyl-3,3-difluoroglutamate
show the reaction diagram
ATP + methotrexate + Glu
ADP + phosphate + methotrexyl-Glu
show the reaction diagram
ATP + methotrexate-Glu + L-glutamate
ADP + methotrexate-Glu2 + phosphate
show the reaction diagram
ATP + methotrexate-Glun + Glu
ADP + phosphate + methotrexyl-Glun+1
show the reaction diagram
ATP + methotrexate-phosphinate + L-glutamate
?
show the reaction diagram
-
-
-
?
ATP + methotrexate-phosphonate + L-glutamate
?
show the reaction diagram
-
-
-
?
ATP + N-(4-(2(2-amino-3,4-dihydro-4-oxo-7H-pyrolo-(2,3-d)pyrimidine-5-yl)ethyl)-benzoyl)-L-glutamic acid + L-glutamate
ADP + N-(4-(2(2-amino-3,4-dihydro-4-oxo-7H-pyrolo-(2,3-d)pyrimidine-5-yl)ethyl)-benzoyl)-L-Glu2 + phosphate
show the reaction diagram
ATP + N-(5-(N-(3,4-dihydro-2-methyl-4-oxoquinazolin-6-ylmethyl)-N-methylamino)-2-thenoyl)L-glutamic acid + L-glutamate
ADP + N-(5-(N-(3,4-dihydro-2-methyl-4-oxoquinazolin-6-ylmethyl)-N-methylamino)-2-thenoyl)L-Glu2 + phosphate
show the reaction diagram
ATP + N-(p(((2-amino-4-hydroxy-6-pteridinyl)methyl)-amino)benzoyl)glutamic acid + L-glutamate
ADP + phosphate + N-(p(((2-amino-4-hydroxy-6-pteridinyl)methyl)-amino)benzoyl)-Glu2
show the reaction diagram
ATP + N-(p(((2-amino-4-hydroxy-6-pteridinyl)methyl)-amino)benzoyl)glutamic acid + L-glutamate
ADP + phosphate + N-(p(((2-amino-4-hydroxy-6-pteridinyl)methyl)-amino)benzoyl)Glu2
show the reaction diagram
-
folic acid, poor substrate
-
?
ATP + Nalpha-(4-amino-4-deoxy-5,8-diazapteroyl)-L-ornithine + L-glutamate
?
show the reaction diagram
-
-
-
?
ATP + Nalpha-(4-amino-4-deoxy-5,chloropteroyl)-L-ornithine + L-glutamate
?
show the reaction diagram
-
-
-
?
ATP + Nalpha-(4-amino-4-deoxy-8-deazapteroyl)-L-ornithine + L-glutamate
?
show the reaction diagram
-
-
-
?
ATP + Nalpha-(4-amino-4-deoxy-N10-methylpteroyl)-Nepsilon-(phosphonoacetyl)-L-lysine + L-glutamate
?
show the reaction diagram
-
much less effective than folic acid
-
?
ATP + Nalpha-(4-amino-4-deoxypteroyl)-Ndelta-hemiphthaloyl-L-ornithine + L-glutamate
?
show the reaction diagram
-
-
-
?
ATP + Nalpha-(5,8-dideaza-5-chloropteroyl)-L-ornithine + L-glutamate
?
show the reaction diagram
-
-
-
?
ATP + Nalpha-(5,8-dideazapteroyl)-L-ornithine + L-glutamate
?
show the reaction diagram
-
-
-
?
ATP + Nalpha-pteroyl-L-ornithine + L-glutamate
?
show the reaction diagram
-
-
-
?
ATP + pemetrexed + Glu
ADP + phosphate + pemetrexyl-Glu
show the reaction diagram
-
-
-
-
?
ATP + pteroyl-(4-aminobutanoyl)-Glu + Glu
ADP + phosphate + pteroyl-(4-aminobutanoyl)-Glu2
show the reaction diagram
-
-
-
-
-
ATP + pteroyl-(5-aminopentanoyl)-Glu + Glu
ADP + phosphate + pteroyl-(5-aminopentanoyl)-Glu2
show the reaction diagram
-
-
-
-
-
ATP + pteroyl-beta-Ala-Glu + Glu
ADP + phosphate + pteroyl-beta-Ala-Glu2
show the reaction diagram
-
-
-
-
-
ATP + pteroyl-Glu + Glu
ADP + phosphate + pteroylmonoglutamyl-Glu
show the reaction diagram
ATP + tetrahydroaminopterin + Glu
ADP + phosphate + tetrahydroaminopteryl-Glu
show the reaction diagram
-
-
-
-
ATP + tetrahydrofolate-Glu + L-glutamate
ADP + phosphate + tetrahydrofolyl-Glu2
show the reaction diagram
ATP + tetrahydropteroyl-[gamma-Glu]n + L-glutamate
ADP + phosphate + tetrahydropteroyl-[gamma-Glu]n+1
show the reaction diagram
-
-
-
?
CTP + 5,6,7,8-tetrahydropteroyl-Glu + Glu
CDP + phosphate + 5,6,7,8-tetrahydropteroyl-Glu2
show the reaction diagram
dATP + 5,10-methylene-5,6,7,8-tetrahydropteroyl-Glu + Glu
dADP + phosphate + 5,10-methylene-5,6,7,8-tetrahydropteroyl-gamma-Glu2
show the reaction diagram
-
-
-
-
dATP + 5,6,7,8-tetrahydropteroyl-Glu + Glu
dADP + phosphate + 5,6,7,8-tetrahydropteroyl-Glu2
show the reaction diagram
dATP + aminopterin + Glu
dADP + phosphate + aminopteryl-Glu
show the reaction diagram
-
112% of the activity relative to ATP
-
-
-
dGTP + aminopterin + Glu
dGDP + phosphate + aminopteryl-Glu
show the reaction diagram
-
37% of the activity relative to ATP
-
-
-
GTP + 5,10-methylene-5,6,7,8-tetrahydropteroyl-gamma-Glu + Glu
GDP + phosphate + 5,10-methylene-5,6,7,8-tetrahydropteroyl-gamma-Glu2
show the reaction diagram
-
-
-
-
ITP + 5,10-methylene-5,6,7,8-tetrahydropteroyl-Glu + Glu
IDP + phosphate + 5,10-methylene-5,6,7,8-tetrahydropteroyl-gamma-Glu2
show the reaction diagram
-
-
-
-
ITP + 5,6,7,8-tetrahydropteroyl-Glu + Glu
IDP + phosphate + 5,6,7,8-tetrahydropteroyl-Glu2
show the reaction diagram
-
-
-
-
-
L-glutamate + ATP + aminopterin
?
show the reaction diagram
-
assay at 37C
-
-
?
UTP + 5,10-methylene-5,6,7,8-tetrahydropteroyl-Glu + Glu
UDP + phosphate + 5,10-methylene-5,6,7,8-tetrahydropteroyl-gamma-Glu2
show the reaction diagram
-
-
-
-
UTP + 5,6,7,8-tetrahydropteroyl-Glu + Glu
UDP + phosphate + 5,6,7,8-tetrahydropteroyl-Glu2
show the reaction diagram
additional information
?
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
ATP + tetrahydrofolate-Glu + L-glutamate
ADP + phosphate + tetrahydrofolyl-Glu2
show the reaction diagram
ATP + tetrahydropteroyl-[gamma-Glu]n + L-glutamate
ADP + phosphate + tetrahydropteroyl-[gamma-Glu]n+1
show the reaction diagram
F4J2K2, F4K2A1
-
-
-
?
additional information
?
-
COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
NaHCO3
Rb+
-
absolute requirement for monovalent cation is met by, inhibition at high concentrations
INHIBITORS
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
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
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
2-mercaptoethanol
3,3-difluoroglutamate
dithiothreitol
-
maximal stimulation at 2.5 mM
pemetrexed
-
treatment of 211-H cells results in significantly higher expression of foloylpolyglutamate synthase and reduced folate carrier 1. Pemetrexed shows potent cytotoxicity in 211-H cells
Reducing agents
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.002 - 0.0029
(6R)-10-formyl-5,6,7,8-tetrahydropteroylglutamate
0.00193
(6R)-5,10-dideaza-5,6,7,8-tetrahydrofolate
-
-
0.00087
(6R)-5,10-dideaza-5,6,7,8-tetrahydropteroyl-L-glutamate-gamma-L-glutamate
-
-
0.00096
(6R)-5,10-dideaza-5,6,7,8-tetrahydropteroyl-L-glutamate-gamma-L-glutamate-gamma-L-glutamate
-
-
0.0016
(6R)-5,10-dideaza-5,6,7,8-tetrahydropteroyl-L-glutamate-gamma-L-glutamate-gamma-L-glutamate-gamma-L-glutamate
-
-
0.00105
(6R)-5,10-dideaza-5,6,7,8-tetrahydropteroyl-L-glutamate-gamma-L-glutamate-gamma-L-glutamate-gamma-L-glutamate-gamma-L-glutamate
-
-
0.0145
(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
-
-
1
(6RS)-5,6,7,8-tetrahydrofolic acid
-
pH 9.75
0.00106
(6S)-5,10-dideaza-5,6,7,8-tetrahydrofolate
-
-
0.00116
(6S)-5,10-dideaza-5,6,7,8-tetrahydropteroyl-L-glutamate-gamma-L-glutamate
-
-
0.0014 - 0.0063
(6S)-5,6,7,8-tetrahydropteroylglutamate
0.075 - 0.122
(6S)-5-formyl-5,6,7,8-tetrahydropteroylglutamate
0.054 - 0.064
(6S)-5-methylene-5,6,7,8-tetrahydropteroylglutamate
0.0022 - 0.014
10-formyl-5,6,7,8-tetrahydropteroyl-Glu
0.41
3,3-difluoroglutamate
-
reaction with methotrexate + ATP
0.0031 - 0.0054
3,3-difluoromethotrexate
0.0012 - 0.0076
5,10-dideazatetrahydrofolic acid
0.03 - 3.8
5,10-methylene-5,6,7,8-tetrahydrofolic acid
0.01 - 0.204
5,10-methylene-5,6,7,8-tetrahydrofolyl-(L-Glu)2
0.0048 - 0.057
5,10-methylene-5,6,7,8-tetrahydropteroyl-Glu
0.0023
5,10-methylene-5,6,7,8-tetrahydropteroyl-Glu2
-
-
0.00123
5,6,7,8-tetrahydrofolate-Glu2
-
pH 8.7
0.01 - 0.655
5,6,7,8-tetrahydrofolic acid
0.3
5,6,7,8-tetrahydrofolyl-gamma-(L-Glu)2
mutant D154A, pH 9.8
0.074
5,6,7,8-tetrahydropteroyl-(4-aminobutanoyl)-Glu
-
-
0.16
5,6,7,8-tetrahydropteroyl-beta-Ala-Glu
-
L-Glu
0.0021 - 6.8
5,6,7,8-tetrahydropteroyl-Glu
0.0033 - 0.0034
5,6,7,8-tetrahydropteroyl-Glu2
0.0011 - 0.0014
5,6,7,8-tetrahydropteroyl-Glu3
0.0016 - 0.002
5,6,7,8-tetrahydropteroyl-Glu4
0.0027
5,6,7,8-tetrahydropteroyl-Glu5
0.0081 - 0.105
5-formyl-5,6,7,8-tetrahydropteroyl-Glu
0.013
5-formyl-5,6,7,8-tetrahydropteroyl-Glu2
-
-
0.444
5-methyl-H4-homofolate
-
-
0.0063 - 0.98
7,8-dihydropteroate
0.012
7,8-dihydropteroyl-(4-aminobutanoyl)-Glu
0.022
7,8-dihydropteroyl-(5-aminopentanoyl)-Glu
-
-
0.076
7,8-dihydropteroyl-beta-Ala-Glu
-
-
0.00081 - 0.0086
7,8-dihydropteroyl-Glu
0.0026 - 0.048
7,8-dihydropteroyl-Glu2
0.004 - 0.18
aminopterin
0.0046 - 35.7
ATP
0.05
dATP
-
reaction with 5,6,7,8-tetrahydropteroyl-Glu + ATP
0.0073
dihydroaminopterin
-
-
0.332 - 5.984
Glu
0.235
glutamic acid
-
pH 8.9, 37C, charcoal assay, wild type recombinant enzyme
0.136
ITP
-
reaction with 5,6,7,8-tetrahydropteroyl-Glu + ATP
0.053 - 150
L-Glu
0.24 - 26.69
L-glutamate
0.43 - 350
L-Glutamic acid
0.019 - 0.138
methotrexate
0.063 - 0.074
methotrexate-Glu
0.029
methotrexate-Glu2
-
-
0.02
methotrexate-Glu3
0.011
methotrexate-Glu4
-
methotrexate-Glu5
0.018 - 5.6
MgATP2-
0.126 - 0.14
N-(p(((2-amino-4-hydroxy-6-pteridinyl)methyl)-amino)benzoyl)glutamic acid
0.81
pteroyl-(4-aminobutanoyl)-Glu
-
-
1.09
pteroyl-(5-aminopentanoyl)-Glu
-
-
0.69
pteroyl-beta-Ala-Glu
-
-
0.059 - 0.137
pteroyl-Glu
0.016
pteroyl-Glu2
-
-
0.119
pteroyl-Glu3
-
-
0.064
pteroyl-Glu5
-
-
0.962
pteroylglutamate
-
-
0.093
pteroylmonoglutamate
-
-
0.062
pteroylmonoglutamyl-Glu
0.00096
tetrahydrofolate
-
-
0.19
UTP
-
reaction with 5,6,7,8-tetrahydropteroyl-Glu + ATP
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.095 - 0.212
(6R)-10-formyl-5,6,7,8-tetrahydropteroylglutamate
0.116 - 0.215
(6S)-5,6,7,8-tetrahydropteroylglutamate
0.073 - 0.115
(6S)-5-formyl-5,6,7,8-tetrahydropteroylglutamate
0.01 - 0.145
5,10-dideazatetrahydrofolic acid
0.99
5,6,7,8-tetrahydropteroyl-Glu
Homo sapiens
-
-
0.81
5,6,7,8-tetrahydropteroyl-Glu2
Homo sapiens
-
-
0.11 - 0.22
5-methyl-5,6,7,8-tetrahydropteroylglutamate
0.84
7,8-dihydropteroyl-Glu
Homo sapiens
-
-
0.95
7,8-dihydropteroyl-Glu2
Homo sapiens
-
-
0.165 - 2
aminopterin
1.7
L-Glu
Sus scrofa
-
-
0.65
pteroyl-Glu
Homo sapiens
-
-
0.82
pteroyl-Glu2
Homo sapiens
-
-
0.55
pteroyl-Glu3
Homo sapiens
-
-
0.34
pteroyl-Glu4
Homo sapiens
-
-
0.01
pteroyl-Glu5
Homo sapiens
-
-
additional information
additional information
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0023 - 0.0052
(6R)-10-formyl-5,6,7,8-tetrahydropteroylpentaglutamate
0.157
(6R)-5,10-dideaza-5,6,7,8-tetrahydropteroyl-L-glutamate-gamma-L-glutamate
-
-
0.179
(6R)-5,10-dideaza-5,6,7,8-tetrahydropteroyl-L-glutamate-gamma-L-glutamate-gamma-L-glutamate-gamma-L-glutamate
-
-
0.144
(6R)-5,10-dideaza-5,6,7,8-tetrahydropteroyl-L-glutamate-gamma-L-glutamate-gamma-L-glutamate-gamma-L-glutamate-gamma-L-glutamate
-
-
0.417
(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
-
-
0.076
(6S)-5,10-dideaza-5,6,7,8-tetrahydrofolate
-
-
0.092
(6S)-5,10-dideaza-5,6,7,8-tetrahydropteroyl-L-glutamate-gamma-L-glutamate
-
-
0.0017 - 0.043
(6S)-5,10-methylene-5,6,7,8-tetrahydropteroylpentaglutamate
0.0037 - 0.054
(6S)-5,6,7,8-tetrahydropteroylpentaglutamate
0.066 - 0.084
(6S)-5-formyl-5,6,7,8-tetrahydropteroylpentaglutamate
0.02 - 0.055
(6S)-5-methyl-5,6,7,8-tetrahydropteroylpentaglutamate
0.00063
2-[[(4-[[(2-amino-4-oxo-3,4-dihydropteridin-6-yl)methyl]amino]phenyl)(hydroxy)phosphoryl]methyl]pentanedioic acid
-
-
0.000091
2-[[[(3S)-3-[(4-[[(2-amino-4-oxo-3,4-dihydropteridin-6-yl)methyl]amino]benzoyl)amino]-3-carboxypropyl](hydroxy)phosphoryl]methyl]pentanedioic acid
-
-
0.00015
4-amino-4-deoxypteroyl-L-ornithine
-
-
0.0000031 - 0.000056
methotrexate-phosphinate
0.000072
Nalpha-(4-amino-4-deoxy-5,8-diazapteroyl)-L-ornithine
-
-
0.0000017
Nalpha-(4-amino-4-deoxy-5,chloropteroyl)-L-ornithine
-
-
0.000018
Nalpha-(4-amino-4-deoxy-8-deazapteroyl)-L-ornithine
-
-
0.0000083
Nalpha-(5,8-dideaza-5-chloropteroyl)-L-ornithine
-
-
0.00035
Nalpha-(5,8-dideazapteroyl)-L-ornithine
-
-
0.0035
Nalpha-pteroyl-L-ornithine
-
-
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.000008 - 13
(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
0.0000012
(S)-2(5-(((1,2-dihydro-3-methyl-1-oxobenzo-(f)quinazolin-9-yl)methyl)-1-oxo-2-isoindolinyl))-glutaric acid
Homo sapiens
-
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
0.00039
2-[[[(3S)-3-[(4-[[(2-amino-4-oxo-3,4-dihydropteridin-6-yl)methyl]amino]benzoyl)amino]-3-carboxypropyl](hydroxy)phosphoryl]methyl]pentanedioic acid
Plasmodium falciparum
-
-
0.000143 - 13
5,10-dideaza-5,6,7,8-tetrahydrofolic acid
0.0000095 - 0.0000175
methotrexate
0.000001 - 13
methotrexate-Glu
0.000008
methotrexate-phosphinate
Homo sapiens
-
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
0.00012
methotrexate-phosphonate
Homo sapiens
-
IC50 0.00012 mM, at fixed substrate and recombinant enzyme concentrations
0.000116 - 13
N-(4-(2(2-amino-3,4-dihydro-4-oxo-7H-pyrolo-(2,3-d)pyrimidine-5-yl)ethyl)-benzoyl)-L-glutamic acid
Mus musculus
-
IC50 of 0.0000136 mM in the wild type cell line, IC50 of 0.000116 mM in the MTA-13 cell line
0.000028 - 13
N-(5-(N-(3,4-dihydro-2-methyl-4-oxoquinazolin-6-ylmethyl)-N-methylamino)-2-thenoyl)L-glutamic acid
0.000006
Nalpha-(4-amino-4-deoxypteroyl)-Ndelta-hemiphthaloyl-L-ornithine
Homo sapiens
-
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
0.000011 - 0.0000302
pemetrexed
additional information
2-[[[(4S)-4-carboxy-4-[(4-[[(2,4-diaminopteridin-6-yl)methyl](methyl)amino]benzoyl)amino]butyl](hydroxy)phosphoryl]methyl]pentanedioic acid
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
0.00000001
-
patients with acute myeloid leukemia, AML
0.00000006
-
enzyme from L44 cells
0.000000099
-
patients with T-linage acute lymphoblastic leukemia, T-ALL
0.0000001
-
enzyme from L15 cells; enzyme from L51 cells; enzyme from L7 cells
0.000000244
-
patients with c/preB-acute lymphoblastic leukemia, c/preB-ALL
0.000001
-
YK01 methionine auxotoph mutant, 5,10-methylene-tetrahydrofolate as a substrate
0.0000015
-
YK01 methionine auxotoph mutant, tetrahydrofolate as a substrate
0.000008
-
wild type enzyme
0.00002458
-
K-562 cells
0.00002625
-
CCRF-CEM cells
0.00003516
-
A-253 cells
0.0000545
-
FaDu cells
0.0003
-
mutant E143A, pH 9.75
0.0005
-
mutant E143Q, pH 9.75
0.00055
-
mutant E143D, pH 9.75
0.0015
-
K185A mutant
0.0043
-
S412A mutant
0.0053
-
E81A mutant
0.008
-
R82A mutant
0.0083
-
supernatant of cell extract
0.0093
-
S73A mutant
0.016
-
ammonium sulfate fraction
0.13
-
Sephacryl S-100 HR fraction
0.16
-
D345C mutant, pH 9.75
0.176
-
double mutant enzyme, pH 9.75
0.18
-
K172C mutant, pH 9.75
0.22
-
DEAE-Sephacel fraction
0.31
-
-
0.465
-
-
0.85
-
-
4.1
substrate 7,8-dihydropteroate, pH 9.8
5.2
-
-
11.8
-
substrate 5,10-methylene-5,6,7,8-tetrahydrofolic acid, pH 9.8
13.2
substrate 5,10-methylene-5,6,7,8-tetrahydrofolic acid, pH 9.8
45.6
-
-
additional information