Information on EC 6.3.2.17 - tetrahydrofolate synthase

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

EC NUMBER
COMMENTARY
6.3.2.17
-
RECOMMENDED NAME
GeneOntology No.
tetrahydrofolate synthase
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
ATP + tetrahydropteroyl-[gamma-Glu]n + L-glutamate = ADP + phosphate + tetrahydropteroyl-[gamma-Glu]n+1
show the reaction diagram
ordered ter-ter mechanism with MgATP binding first, folate second and Glu last
-
ATP + tetrahydropteroyl-[gamma-Glu]n + L-glutamate = ADP + phosphate + tetrahydropteroyl-[gamma-Glu]n+1
show the reaction diagram
formation of a pteroyl-gamma-glutamyl phosphate intermediate
-
ATP + tetrahydropteroyl-[gamma-Glu]n + L-glutamate = ADP + phosphate + tetrahydropteroyl-[gamma-Glu]n+1
show the reaction diagram
the products are released in the order: ADP, 5,6,7,8-tetrahydropteroyl-Glu2, phosphate
-
ATP + tetrahydropteroyl-[gamma-Glu]n + L-glutamate = ADP + phosphate + tetrahydropteroyl-[gamma-Glu]n+1
show the reaction diagram
ordered ter ter mechanism with MgATP binding first to the enzyme, folate second, and glutamate last
-
ATP + tetrahydropteroyl-[gamma-Glu]n + L-glutamate = ADP + phosphate + tetrahydropteroyl-[gamma-Glu]n+1
show the reaction diagram
ordered ter ter mechanism with MgATP binding first to the enzyme, folate second, and glutamate last
-
ATP + tetrahydropteroyl-[gamma-Glu]n + L-glutamate = ADP + phosphate + tetrahydropteroyl-[gamma-Glu]n+1
show the reaction diagram
sequential mechanism
-
ATP + tetrahydropteroyl-[gamma-Glu]n + L-glutamate = ADP + phosphate + tetrahydropteroyl-[gamma-Glu]n+1
show the reaction diagram
processive mechanism, in which the folate is the first substrate to bind and the folate-Glu product is the last to be released
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
carboxamide formation
-
-
-
-
carboxylic acid amide formation
-
-
-
-
PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
Folate biosynthesis
-
-
folate polyglutamylation
-
-
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.
SYNONYMS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Folate polyglutamate synthetase
-
-
-
-
Folylpoly(.gamma.-glutamate) synthase
-
-
-
-
Folylpoly-.gamma.-glutamate synthase
-
-
-
-
Folylpoly-gamma-glutamate synthetase
-
-
-
-
Folylpoly-gamma-glutamate synthetase-dihydrofolate synthetase
-
-
-
-
Folylpolyglutamate synthase
-
-
-
-
Folylpolyglutamate synthetase
-
-
-
-
Folylpolyglutamyl synthetase
-
-
-
-
Formyltetrahydropteroyldiglutamate synthetase
-
-
-
-
FPGS
-
-
-
-
N10-Formyltetrahydropteroyldiglutamate synthetase
-
-
-
-
Synthetase, folylpolyglutamate
-
-
-
-
Tail length regulator
-
-
-
-
tetrahydrofolate:L-glutamate gamma-ligase (ADP-forming)
-
-
-
-
tetrahydrofolylpolyglutamate synthase
-
-
-
-
CAS REGISTRY NUMBER
COMMENTARY
63363-84-8
-
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
DFC; gene dfc encoding isozyme DFC
UniProt
Manually annotated by BRENDA team
ecotype Wassilewskija
-
-
Manually annotated by BRENDA team
FPGS1; gene dfb encoding isozyme FPGS1
UniProt
Manually annotated by BRENDA team
high expression
-
-
Manually annotated by BRENDA team
strain BL21(DE3)
-
-
Manually annotated by BRENDA team
human, children
-
-
Manually annotated by BRENDA team
patients with colorectal cancer
-
-
Manually annotated by BRENDA team
recombinant
-
-
Manually annotated by BRENDA team
wild type and met-9 mutant
-
-
Manually annotated by BRENDA team
wild type FGSC 853, mutant met-6, 35809 (FGSC 1330) and mutant mac, 65108 (FGSC 3609)
-
-
Manually annotated by BRENDA team
3D7, K1, Tak9, M24, K39, HB3, W282, V1/S, Dd2 and FCB lines
-
-
Manually annotated by BRENDA team
pig
-
-
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
-
disruption of FPGS leads to short primary roots and root hairs. Phenotype is associated with a disorganized quiescent center, dissipated auxin gradient in the root cap, bundled actin cytoskeleton, and reduced cell division and expansion. The root growth and quiescent center defects of mutant are rescued by exogenous application of 5-formyl-tetrahydrofolate
malfunction
F4J2K2, F4K2A1
deficiency in N utilization in an Arabidopsis thaliana transfer DNA insertion mutant of the mitochondrial folylpolyglutamate synthetase gene DFC. The mutant seedlings display several metabolic changes that are typical of plant responses to low-N stress, including increased levels of starch and anthocyanin synthesis as well as decreased levels of soluble protein and free amino acid, as compared to wild-type seedlings with sufficient external N. Isozyme FPGS1 can partially compensate for isozyme DFC defect. No significant differences in growth, development, or fertility are observed between wild-type and dfc plants in soil
malfunction
F4J2K2, F4K2A1
isozyme FPGS1 can partially compensate for isozyme DFC defect
physiological function
-
the mitochondrial folylpolyglutamate synthetase catalyzes the conjugation of glutamate residues to the tetrahydrofolate during folate synthesis
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
additional information
-
folate profiles in Arabidopsis seedlings, overview
SUBSTRATE
PRODUCT                      
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
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-L-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-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
-
-
-
-
ir
ATP + (6RS)-5,6,7,8-tetrahydrofolic acid + L-glutamate
ADP + phosphate + (6S)-5,6,7,8-tetrahydrofolyl-Glu
show the reaction diagram
-
not as effective as 5,10-methylene-5,6,7,8-tetrahydrofolic acid
-
?
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)-5,6,7,8-tetrahydropteroylglutamate + L-glutamate
ADP + phosphate + (6S)-5,6,7,8-tetrahydropteroyl-Glu2
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)-5,6,7,8-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-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-tetrahydropteroyl-Glu + Glu
ADP + phosphate + 10-formyl-5,6,7,8-tetrahydropteroyl-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-tetrahydropteroyl-Glu + Glu
ADP + phosphate + 10-formyl-5,6,7,8-tetrahydropteroyl-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-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-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-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
-
lometrexol
-
?
ATP + 5,10-dideazatetrahydrofolic acid + L-glutamate
ADP + 5,10-dideazatetrahydrofolyl-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
P08192
-
-
-
?
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-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-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-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-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-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-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
-
n: 3
-
-
-
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
-
n: 3
-
-
-
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
-
n: 5
-
-
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
-
n: 2
-
-
-
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
-
n: 2
-
-
-
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
-
n: 7, n: 6
-
-
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
-
n:1
-
-
-
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
-
n:1
-
-
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
-
n:1
-
-
-
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
-
n:1
-
-
-
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
-
n:1
-
-
-
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
-
n:1
-
-
-
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-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
P08192
-
-
-
?
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-tetrahydrofolic acid + L-glutamate
ADP + phosphate + 5,6,7,8-tetrahydrofolyl-Glu
show the reaction diagram
P15925
-
-
?
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
P08192
-
-
-
?
ATP + 5,6,7,8-tetrahydropteroate + Glu
ADP + phosphate + 5,6,7,8-terahydropteroyl-Glu
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-4-aminobutanoyl-Glu + Glu
ADP + phosphate + 5,6,7,8-tetrahydropteroyl-4-aminobutanoyl-Glun
show the reaction diagram
-
-
n: 3-5
-
ATP + 5,6,7,8-tetrahydropteroyl-gamma-Glu + Glu
ADP + phosphate + 5,6,7,8-tetrahydropteroyl-gamma-Glu2
show the reaction diagram
-
gaba i.e. gamma-aminobutanoyl
-
-
-
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-Glun + Glu
ADP + phosphate + 5,6,7,8-tetrahydropteroyl-gamma-Glun+1
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-Glun + Glu
ADP + phosphate + 5,6,7,8-tetrahydropteroyl-gamma-Glun+1
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
-
n: 3
-
-
-
ATP + 5,6,7,8-tetrahydropteroyl-Glun + Glu
ADP + phosphate + 5,6,7,8-tetrahydropteroyl-gamma-Glun+1
show the reaction diagram
-
n: 3
-
-
-
ATP + 5,6,7,8-tetrahydropteroyl-Glun + Glu
ADP + phosphate + 5,6,7,8-tetrahydropteroyl-gamma-Glun+1
show the reaction diagram
-
n: 5
-
-
-
ATP + 5,6,7,8-tetrahydropteroyl-Glun + Glu
ADP + phosphate + 5,6,7,8-tetrahydropteroyl-gamma-Glun+1
show the reaction diagram
-
n: 2
-
-
-
ATP + 5,6,7,8-tetrahydropteroyl-Glun + Glu
ADP + phosphate + 5,6,7,8-tetrahydropteroyl-gamma-Glun+1
show the reaction diagram
-
n: 2
-
-
-
ATP + 5,6,7,8-tetrahydropteroyl-Glun + Glu
ADP + phosphate + 5,6,7,8-tetrahydropteroyl-gamma-Glun+1
show the reaction diagram
-
n: 1
-
-
-
ATP + 5,6,7,8-tetrahydropteroyl-Glun + Glu
ADP + phosphate + 5,6,7,8-tetrahydropteroyl-gamma-Glun+1
show the reaction diagram
-
n: 1
-
-
-
ATP + 5,6,7,8-tetrahydropteroyl-Glun + Glu
ADP + phosphate + 5,6,7,8-tetrahydropteroyl-gamma-Glun+1
show the reaction diagram
-
n: 1
-
-
-
ATP + 5,6,7,8-tetrahydropteroyl-Glun + Glu
ADP + phosphate + 5,6,7,8-tetrahydropteroyl-gamma-Glun+1
show the reaction diagram
-
n: 1
-
-
-
ATP + 5,6,7,8-tetrahydropteroyl-Glun + Glu
ADP + phosphate + 5,6,7,8-tetrahydropteroyl-gamma-Glun+1
show the reaction diagram
-
n: 1
-
-
-
ATP + 5,6,7,8-tetrahydropteroyl-Glun + Glu
ADP + phosphate + 5,6,7,8-tetrahydropteroyl-gamma-Glun+1
show the reaction diagram
-
n: 1
-
-
-
ATP + 5,6,7,8-tetrahydropteroyl-Glun + Glu
ADP + phosphate + 5,6,7,8-tetrahydropteroyl-gamma-Glun+1
show the reaction diagram
-
n: 1
-
-
-
ATP + 5,6,7,8-tetrahydropteroyl-Glun + Glu
ADP + phosphate + 5,6,7,8-tetrahydropteroyl-gamma-Glun+1
show the reaction diagram
-
n: 1
-
-
-
ATP + 5,6,7,8-tetrahydropteroyl-Glun + Glu
ADP + phosphate + 5,6,7,8-tetrahydropteroyl-gamma-Glun+1
show the reaction diagram
-
n: 4
-
-
-
ATP + 5,6,7,8-tetrahydropteroyl-Glun + Glu
ADP + phosphate + 5,6,7,8-tetrahydropteroyl-gamma-Glun+1
show the reaction diagram
-
n: 7
-
-
-
ATP + 5,6,7,8-tetrahydropteroyl-Glun + Glu
ADP + phosphate + 5,6,7,8-tetrahydropteroyl-gamma-Glun+1
show the reaction diagram
-
n: 6
-
-
-
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-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-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-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-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-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-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-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-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-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-tetrahydropteroyl-gamma-Glun + Glu
ADP + phosphate + 5-methyl-5,6,7,8-tetrahydropteroyl-gamma-Glun+1
show the reaction diagram
-
n: 2
-
-
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
-
n: 1
-
-
-
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
-
n: 1
-
-
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
-
n: 1
-
-
-
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
-
n: 1
-
-
-
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
-
n: 1
-
-
-
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
-
n: 1
-
-
-
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 + 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 + 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
P08192
-
-
-
?
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 + 7,8-dihydropteroyl-Glun + Glu
ADP + phosphate + 7,8-dihydropteroyl-Glun+1
show the reaction diagram
-
n: 5
-
-
ATP + 7,8-dihydropteroyl-Glun + Glu
ADP + phosphate + 7,8-dihydropteroyl-Glun+1
show the reaction diagram
-
n: 5
-
-
-
ATP + 7,8-dihydropteroyl-Glun + Glu
ADP + phosphate + 7,8-dihydropteroyl-Glun+1
show the reaction diagram
-
n: 2
-
-
ATP + 7,8-dihydropteroyl-Glun + Glu
ADP + phosphate + 7,8-dihydropteroyl-Glun+1
show the reaction diagram
-
n: 2
-
-
-
ATP + 7,8-dihydropteroyl-Glun + Glu
ADP + phosphate + 7,8-dihydropteroyl-Glun+1
show the reaction diagram
-
n: 1
-
-
-
ATP + 7,8-dihydropteroyl-Glun + Glu
ADP + phosphate + 7,8-dihydropteroyl-Glun+1
show the reaction diagram
-
n: 1
-
-
-
ATP + 7,8-dihydropteroyl-Glun + Glu
ADP + phosphate + 7,8-dihydropteroyl-Glun+1
show the reaction diagram
-
n: 1
-
-
-
ATP + 7,8-dihydropteroyl-Glun + Glu
ADP + phosphate + 7,8-dihydropteroyl-Glun+1
show the reaction diagram
-
n: 1
-
-
ATP + 7,8-dihydropteroyl-Glun + Glu
ADP + phosphate + 7,8-dihydropteroyl-Glun+1
show the reaction diagram
-
n: 1
-
-
-
ATP + 7,8-dihydropteroyl-Glun + Glu
ADP + phosphate + 7,8-dihydropteroyl-Glun+1
show the reaction diagram
-
n: 1
-
-
-
ATP + 7,8-dihydropteroyl-Glun + Glu
ADP + phosphate + 7,8-dihydropteroyl-Glun+1
show the reaction diagram
-
n: 1
-
-
-
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 + Glu
ADP + phosphate + aminopteryl-Glu
show the reaction diagram
-
-
-
-
-
ATP + aminopterin + Glu
ADP + phosphate + aminopteryl-Glu
show the reaction diagram
-
-
-
-
-
ATP + aminopterin + Glu
ADP + phosphate + aminopteryl-Glu
show the reaction diagram
-
-
-
-
-
ATP + aminopterin + Glu
ADP + phosphate + aminopteryl-Glu
show the reaction diagram
-
-
-
-
-
ATP + aminopterin + Glu
ADP + phosphate + aminopteryl-Glu
show the reaction diagram
-
-
-
-
-
ATP + aminopterin + Glu
ADP + phosphate + aminopteryl-Glu
show the reaction diagram
-
-
products with a glutamate chain length of 2-4 are formed
-
ATP + aminopterin + Glu
ADP + phosphate + aminopteryl-Glu
show the reaction diagram
-
most active substrate
-
-
-
ATP + aminopterin + L-glutamate
?
show the reaction diagram
-
-
-
?
ATP + aminopterin + L-glutamate
?
show the reaction diagram
-
-
-
?
ATP + aminopterin + L-glutamate
?
show the reaction diagram
-
-
-
?
ATP + aminopterin + L-glutamate
?
show the reaction diagram
-
more efficient than 6-S 5,10-dideaza-5,6,7,8-tetrahydrofolate-Glu2 and 6-R 5,10-dideaza-5,6,7,8-tetrahydrofolate-Glu2, recombinant enzyme from leukemic cells
-
?
ATP + dichloromethotrexate + Glu
ADP + phosphate + dichloromethotrexyl-Glu
show the reaction diagram
-
-
-
-
-
ATP + dihydroaminopterin + Glu
ADP + phosphate + dihydroaminopteryl-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 + 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
ADP + phosphate + methotrexyl-Glu
show the reaction diagram
-
-
-
-
ATP + methotrexate + Glu
ADP + phosphate + methotrexyl-Glu
show the reaction diagram
-
-
-
-
-
ATP + methotrexate + Glu
ADP + phosphate + methotrexyl-Glu
show the reaction diagram
-
-
-
-
?
ATP + methotrexate + Glu
ADP + phosphate + methotrexyl-Glu
show the reaction diagram
-
-
-
-
-
ATP + methotrexate + Glu
ADP + phosphate + methotrexyl-Glu
show the reaction diagram
-
-
-
-
ATP + methotrexate + Glu
ADP + phosphate + methotrexyl-Glu
show the reaction diagram
-
-
-
-
-
ATP + methotrexate + Glu
ADP + phosphate + methotrexyl-Glu
show the reaction diagram
-
-
-
-
-
ATP + methotrexate + Glu
ADP + phosphate + methotrexyl-Glu
show the reaction diagram
-
-
-
-
-
ATP + methotrexate + Glu
ADP + phosphate + methotrexyl-Glu
show the reaction diagram
-
weak
-
-
-
ATP + methotrexate-Glu + L-glutamate
ADP + methotrexate-Glu2 + phosphate
show the reaction diagram
-
-
-
?
ATP + methotrexate-Glu + L-glutamate
ADP + methotrexate-Glu2 + phosphate
show the reaction diagram
-
-
-
-
-
ATP + methotrexate-Glu + L-glutamate
ADP + methotrexate-Glu2 + phosphate
show the reaction diagram
-
-
-
?
ATP + methotrexate-Glu + L-glutamate
ADP + methotrexate-Glu2 + phosphate
show the reaction diagram
-
-
-
?
ATP + methotrexate-Glu + L-glutamate
ADP + methotrexate-Glu2 + phosphate
show the reaction diagram
-
-
-
?
ATP + methotrexate-Glu + L-glutamate
ADP + methotrexate-Glu2 + phosphate
show the reaction diagram
-
CHO cells expressing the human enzyme accumulate more metabolized drug than CHO cells expressing equivalent levels of endogenous hamster enzyme. Cells expressing only the mitochondrial isozyme do not metabolize this substrate
-
?
ATP + methotrexate-Glu + L-glutamate
ADP + methotrexate-Glu2 + phosphate
show the reaction diagram
-
T-ALL and AML patients show inefficient polyglutamylation due to lower enzyme activity
-
?
ATP + methotrexate-Glun + Glu
ADP + phosphate + methotrexyl-Glun+1
show the reaction diagram
-
n: 3, n: 5, n:4, n: 2
-
-
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-(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
-
pemetrexed
-
?
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-(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
-
raltitrexed
-
?
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 + 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
-
?
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
-
?
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 + pteroyl-Glu + Glu
ADP + phosphate + pteroylmonoglutamyl-Glu
show the reaction diagram
-
-
-
-
-
ATP + pteroyl-Glu + Glu
ADP + phosphate + pteroylmonoglutamyl-Glu
show the reaction diagram
-
-
-
-
-
ATP + pteroyl-Glu + Glu
ADP + phosphate + pteroylmonoglutamyl-Glu
show the reaction diagram
-
n: 3
-
-
-
ATP + pteroyl-Glu + Glu
ADP + phosphate + pteroylmonoglutamyl-Glu
show the reaction diagram
-
n: 5, n: 2
-
-
-
ATP + pteroyl-Glu + Glu
ADP + phosphate + pteroylmonoglutamyl-Glu
show the reaction diagram
-
n: 2
-
-
-
ATP + pteroyl-Glu + Glu
ADP + phosphate + pteroylmonoglutamyl-Glu
show the reaction diagram
-
n: 2
-
-
-
ATP + pteroyl-Glu + Glu
ADP + phosphate + pteroylmonoglutamyl-Glu
show the reaction diagram
-
n: 4, n: 7, n: 6
-
-
-
ATP + pteroyl-Glu + Glu
ADP + phosphate + pteroylmonoglutamyl-Glu
show the reaction diagram
-
n: 1, i.e. pteroylmonoglutamate, folic acid
-
-
-
ATP + pteroyl-Glu + Glu
ADP + phosphate + pteroylmonoglutamyl-Glu
show the reaction diagram
-
n: 1, i.e. pteroylmonoglutamate, folic acid
-
-
ATP + pteroyl-Glu + Glu
ADP + phosphate + pteroylmonoglutamyl-Glu
show the reaction diagram
-
n: 1, i.e. pteroylmonoglutamate, folic acid
-
-
-
ATP + pteroyl-Glu + Glu
ADP + phosphate + pteroylmonoglutamyl-Glu
show the reaction diagram
-
n: 1, i.e. pteroylmonoglutamate, folic acid
-
-
-
ATP + pteroyl-Glu + Glu
ADP + phosphate + pteroylmonoglutamyl-Glu
show the reaction diagram
-
n: 1, i.e. pteroylmonoglutamate, folic acid
-
-
ATP + pteroyl-Glu + Glu
ADP + phosphate + pteroylmonoglutamyl-Glu
show the reaction diagram
-
n: 1, i.e. pteroylmonoglutamate, folic acid
-
-
ATP + pteroyl-Glu + Glu
ADP + phosphate + pteroylmonoglutamyl-Glu
show the reaction diagram
-
n: 1, i.e. pteroylmonoglutamate, folic acid
-
-
-
ATP + pteroyl-Glu + Glu
ADP + phosphate + pteroylmonoglutamyl-Glu
show the reaction diagram
-
n: 1, i.e. pteroylmonoglutamate, folic acid
-
-
-
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 + 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
-
-
-
?
CTP + 5,6,7,8-tetrahydropteroyl-Glu + Glu
CDP + phosphate + 5,6,7,8-tetrahydropteroyl-Glu2
show the reaction diagram
-
-
-
-
-
CTP + 5,6,7,8-tetrahydropteroyl-Glu + Glu
CDP + phosphate + 5,6,7,8-tetrahydropteroyl-Glu2
show the reaction diagram
-
at 13% of the activity relative to ATP
-
-
-
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 + 5,6,7,8-tetrahydropteroyl-Glu + Glu
dADP + phosphate + 5,6,7,8-tetrahydropteroyl-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
-
as effective as ATP
-
-
-
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
-
-
-
-
-
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
-
-
-
-
-
UTP + 5,6,7,8-tetrahydropteroyl-Glu + Glu
UDP + phosphate + 5,6,7,8-tetrahydropteroyl-Glu2
show the reaction diagram
-
-
-
-
-
L-glutamate + ATP + aminopterin
?
show the reaction diagram
-
assay at 37C
-
-
?
additional information
?
-
-
-
-
-
-
additional information
?
-
-
-
-
-
-
additional information
?
-
-
dATP and UTP can act as substrate
-
-
-
additional information
?
-
-
enzyme also posseses dihydrofolate synthetase activity
-
-
-
additional information
?
-
-
enzyme also posseses dihydrofolate synthetase activity
-
-
-
additional information
?
-
-
pteroate and pteroylmonoglutamate substrates are utilized much more effectively than the polyglutamate derivatives. The most effective substrates are: 5,6,7,8-tetrahydropteroate, tetrahydrofolate, 5,10-methylene-tetrahydrofolate. The most effective diglutamate substrate is : 5,10-methylene-5,6,7,8-tetrahydropteroyldiglutamate
-
-
-
additional information
?
-
-
most effective substrates are: 7,8-dihydrofolate, 5,6,7,8-tetrahydrofolate, 5,10-methylenetetrahydrofolate, 10-formyltetrahydrofolate, 5-formyltetrahydrofolate
-
-
-
additional information
?
-
-
uses 5,10-methylenen-5,6,7,8-tetrahydropteroylpolyglutamate as the preferred, and sometimes only polyglutamate substrate
-
-
-
additional information
?
-
-
folylpolyglutamate synthesis is not mediated by a single enzyme, but by at least two soluble enzymes which are products of the mac and met-6 loci respectively
-
-
-
additional information
?
-
-
no dihydrofolate synthetase activity
-
-
-
additional information
?
-
-
no dihydrofolate synthetase activity
-
-
-
additional information
?
-
-
no dihydrofolate synthetase activity
-
-
-
additional information
?
-
-
no dihydrofolate synthetase activity
-
-
-
additional information
?
-
-
monoglutamyl form and polyglutamyl forms of 5,6,7,8-tetrahydropteroate are the preferred substrates
-
-
-
additional information
?
-
-
alterations in the amino terminal structure of the enzyme may influence its catalytic and/or substrate binding properties
-
?
additional information
?
-
-
depressed activity of the enzyme is the predominant mechanism of high level resistance to polyglutamylation-dependent antifolates
-
?
additional information
?
-
-
met7 mutant strain is a methionine auxotroph and an adenine and thymidine auxotroph when grown in the presence of sulfanilamide. Met7 mutants have a petite phenotype, defective in mitochondrial respiration and unable to grow on glycerol or other nonfermentable substrates as a carbon/energy source. Disruption of met7 causes deficiencies in folate metabolism and loss of both cytoplasmic and mitochondrial enzyme activity. Met7 mutants are complemented by genes that express only cytoplasmic enzyme
-
?
additional information
?
-
-
mitochondrial enzyme activity is required for mitochondrial folate accumulation, and cells lacking this isozyme are auxotrophic for glycine. Overexpression of cytosolic enzyme does not complement the lack of mitochondrial activity
-
?
additional information
?
-
-
the expression of the enzyme in Escherichia coli and Saccharomyces cerevisiae defective strains restores Escherichia coli cells to methionine and glycine prototrophy on minimal medium, but cannot entirely compensate for the loss of the native homologue in Saccharomyces cerevisiae. The malarial gene encodes a protein carrying dihydrofolate synthetase and folylpolyglutamate synthetase activities, both needed for the de novo folate synthesis
-
?
additional information
?
-
-
enzyme catalyzes the addition of glutamate residues to folates and antifolates to form the physiological active coenzymatic forms of the vitamin and more potent anti-folate agents
-
-
-
additional information
?
-
-
enzyme in biosynthesis of folylpolyglutamates , the most universal functions of folylpolyglutamates: 1. Actual cofactors in vivo for folate dependent enzymes, 2. Inhibitor of folate dependent enzymes for which they are not substrates, 3. Increases retention of folates after they are transported into cells as monoglutamates
-
-
-
additional information
?
-
-
mitochondrial enzyme is required for mitochondrial one carbon metabolism and for normal one carbon flux in the cytosol
-
-
-
additional information
?
-
-
enzyme of folate biosynthetic pathway
-
-
-
additional information
?
-
-
central enzyme in establishing and maintaining folylpolyglutamate pools in whole cells
-
?
additional information
?
-
-
the enzyme catalyzes the consecutive addition of one or more L-glutamyl moieties to the gamma-carboxyl group in natural folates and glutamate-containing antifolates. Cells deficient in this enzyme are auxothrophic for thymidine and a purine
-
?
additional information
?
-
-
the enzyme catalyzes the formation of an amide bond between glutamic acid and the gamma-carboxyl group of any of the naturally occurring folate compounds
-
?
additional information
?
-
-
the enzyme catalyzes the formation of polyglutamates from folates and folate antimetabolites in mammalian cells
-
?
additional information
?
-
-
the enzyme catalyzes the MgATP-dependent addition of glutamate residues to the gamma-carboxyl of folates to generate folylpolyglutamates
-
?
additional information
?
-
-
the enzyme catalyzes the MgATP-dependent ligation of L-glutamate to tetrahydrofolate coenzymes or to antifolates at the gamma-carboxyl of the terminal glutamate to form polyglutamate derivatives
-
?
additional information
?
-
-
the enzyme metabolizes tetrahydrofolates to long chain polyglutamates within the cytosol or mitochondria of the cells as a mechanism to trap them within the cell
-
?
additional information
?
-
-
the enzyme metabolizes tetrahydrofolates to long chain polyglutamates within the cytosol or mitochondria of the cells as a mechanism to trap them within the cell
-
?
additional information
?
-
-
the enzyme synthesizes folate and antifolate poly(gamma-glutamate) metabolites
-
?
additional information
?
-
-
there are two possible sites for binding folate substrates. The di- and triglutamate substrates can be accommodated in both sites in a way appropriate for the ligation reaction, but only the new pocket appears to bind mTHF and allow the initial ligation reaction. It is suggested that the new pocket plays an essential role in the first turnover to create folylpoly-glutamates
-
-
-
additional information
?
-
-
folylpoly-gamma-glutamate synthetase can catalyze the processive addition of approximately four glutamate residues to (6R)-5,10-dideaza-5,6,7,8-tetrahydropteroylglutamic acid. The degree of processivity is dependent on the concentration of the folate substrate, thus suggesting a mechanism for the regulation of folate polyglutamate synthesis in cells
-
-
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
ATP + tetrahydrofolate-Glu + L-glutamate
ADP + phosphate + tetrahydrofolyl-Glu2
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
F4J2K2, F4K2A1
-
-
-
?
additional information
?
-
-
enzyme catalyzes the addition of glutamate residues to folates and antifolates to form the physiological active coenzymatic forms of the vitamin and more potent anti-folate agents
-
-
-
additional information
?
-
-
enzyme in biosynthesis of folylpolyglutamates , the most universal functions of folylpolyglutamates: 1. Actual cofactors in vivo for folate dependent enzymes, 2. Inhibitor of folate dependent enzymes for which they are not substrates, 3. Increases retention of folates after they are transported into cells as monoglutamates
-
-
-
additional information
?
-
-
mitochondrial enzyme is required for mitochondrial one carbon metabolism and for normal one carbon flux in the cytosol
-
-
-
additional information
?
-
-
enzyme of folate biosynthetic pathway
-
-
-
additional information
?
-
-
central enzyme in establishing and maintaining folylpolyglutamate pools in whole cells
-
?
additional information
?
-
-
the enzyme catalyzes the consecutive addition of one or more L-glutamyl moieties to the gamma-carboxyl group in natural folates and glutamate-containing antifolates. Cells deficient in this enzyme are auxothrophic for thymidine and a purine
-
?
additional information
?
-
-
the enzyme catalyzes the formation of an amide bond between glutamic acid and the gamma-carboxyl group of any of the naturally occurring folate compounds
-
?
additional information
?
-
-
the enzyme catalyzes the formation of polyglutamates from folates and folate antimetabolites in mammalian cells
-
?
additional information
?
-
-
the enzyme catalyzes the MgATP-dependent addition of glutamate residues to the gamma-carboxyl of folates to generate folylpolyglutamates
-
?
additional information
?
-
-
the enzyme catalyzes the MgATP-dependent ligation of L-glutamate to tetrahydrofolate coenzymes or to antifolates at the gamma-carboxyl of the terminal glutamate to form polyglutamate derivatives
-
?
additional information
?
-
-
the enzyme metabolizes tetrahydrofolates to long chain polyglutamates within the cytosol or mitochondria of the cells as a mechanism to trap them within the cell
-
?
additional information
?
-
-
the enzyme metabolizes tetrahydrofolates to long chain polyglutamates within the cytosol or mitochondria of the cells as a mechanism to trap them within the cell
-
?
additional information
?
-
-
the enzyme synthesizes folate and antifolate poly(gamma-glutamate) metabolites
-
?
additional information
?
-
-
folylpoly-gamma-glutamate synthetase can catalyze the processive addition of approximately four glutamate residues to (6R)-5,10-dideaza-5,6,7,8-tetrahydropteroylglutamic acid. The degree of processivity is dependent on the concentration of the folate substrate, thus suggesting a mechanism for the regulation of folate polyglutamate synthesis in cells
-
-
-
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
ATP
F4J2K2, F4K2A1
;
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
K+
-
Km: 1.6 mM; required form maximal activity
K+
-
absolutely dependent on monovalent cation, K+ is most effective; inhibition at high concentrations
K+
-
absolutely dependent on monovalent cation, K+ is most effective; maximal activity at 200 mM; required form maximal activity
K+
-
maximal activity at 10-20 mM
K+
-
absolutely dependent on monovalent cation, K+ is most effective
K+
-
absolutely dependent on monovalent cation, K+ is most effective; maximal activity at 200 mM
K+
-
maximal activity at 200 mM; required form maximal activity
K+
-
absolutely dependent on monovalent cation, K+ is most effective; maximal activity at 200 mM
K+
-
absolutely dependent on monovalent cation, K+ is most effective
K+
-
maximal activity at 200 mM; required form maximal activity
K+
-
maximal activity at 200 mM; required form maximal activity
K+
-
maximal activity at 20 mM; required form maximal activity
K+
-
maximal activity at 200 mM; required form maximal activity
K+
-
maximal activity at 20 mM; required form maximal activity
K+
-
maximal activity at 200 mM; maximal activity at 20 mM; required form maximal activity
Mg2+
-
Km: 3.7 mM; required
Mg2+
-
in presence of 0.1 mM ATP, maximal activity at 2 mM Mg2+; required
Mg2+
-
MgATP2- is an effective substrate
Mg2+
-
optimal Mg2+ concentration is dependent on ATP concentration; required
Mg2+
-
-
Mg2+
-
required
Mg2+
-
required
Mg2+
-
required
Mg2+
-
maximal activity at 20 mM; required
Mg2+
-
essential
Mn2+
-
supports activity, at 1 mM 68% of the activity obtained with Mg2+
Mn2+
-
MnATP2- is an effective substrate
Mn2+
-
stimulates
NaHCO3
-
activates
NaHCO3
-
optimal activation at 10 mM
NH4+
-
inhibition by high concentrations; stimulates to a lesser extent than K+
NH4+
-
stimulates to a lesser extent than K+
Rb+
-
absolute requirement for monovalent cation is met by, inhibition at high concentrations
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY
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
-
IC50 of 0.0000153 mM in the wild type cell line, IC50 of 0.000008 mM to 0.0016 mM in the antifolates-resistant sublines
(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
-
IC50 of 0.0000125 mM in the wild type cell line, IC50 of 0.0000635 mM in the MTA-13 cell line
(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
-
i.e. beta,beta-difluoroglutamate, , the effect on polyglutamylation is dependent on its position relative to the point of L-Glu ligation. When beta,beta-difluoroglutamate is the acceptor amino acid, i.e. point of attachment. Ligation of Glu is enhanced. When beta,beta-difluoroglutamate is one residue distal to the acceptor amino acid, further elongation is blocked
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
-
IC50 of 0.0000277 mM in the wild type cell line, IC50 of 0.000143 mM to 0.0035 mM in the antifolates-resistant sublines
5,10-dideaza-5,6,7,8-tetrahydrofolic acid
-
IC50 of 0.0000591 mM in the wild type cell line, IC50 of 0.000205 mM in the MTA-13 cell line
5,10-dideaza-5,6,7,8-tetrahydrofolic acid
-
lometrexo, used to generate the 5,10-dideazatetrahydrofolate resistant cells sublines
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
-
inhibits reaction with 5,6,7,8-tetrahydropteroyl-Glu + ATP and pteroylmonoglutamate + ATP
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)
-
-
ADP
-
-
ADP
-
noncompetitive with respect to MgATP2-
ADP
-
-
aminopterin
-
inhibits reaction with pteroylmonoglutamate + ATP
aminopterin
-
-
aminopterin
-
5,6,7,8-tetrahydropteroyl-Glu2 formation
AMP
-
-
AMP
-
-
ATP4-
-
-
beta,gamma-Imido-ATP
-
-
beta,gamma-methylene-ATP
-
-
beta,gamma-methylene-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
-
weak, competitive with respect to MgATP2-
diphosphate
-
-
Endogenous inhibitor from Neurospora crassa
-
the inhibitor is present in either polyglutamate-deficient mutants and in wild type. This factor is non-dialyzable, thermolabile and inactivated by urea and trypsin treatment
-
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
-
-
L-Homocysteate
-
prevents or severly retards further addition of Glu
methotrexate
-
the level required to inhibit the 5,10-dideazatetrahydrofolate resistant cell sublines is unchanged or slightly decreased compared with wild type cells
methotrexate
-
-
methotrexate-Glu
-
IC50 of 0.0000014 mM in the wild type cell line, IC50 of 0.000001 mM to 0.00095 mM in the antifolates-resistant sublines
methotrexate-Glu
-
IC50 of 0.00002 mM in the wild type cell line, IC50 of 0.0000545 mM in the MTA-13 cell line
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
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
-
IC50 of 0.0000032 mM in the wild type cell line, IC50 of 0.00032 mM to 0.007168 mM in the antifolates-resistant sublines
N-(5-(N-(3,4-dihydro-2-methyl-4-oxoquinazolin-6-ylmethyl)-N-methylamino)-2-thenoyl)L-glutamic acid
-
IC50 of 0.0000033 mM in the wild type cell line, IC50 of 0.000028 mM in the MTA-13 cell line
N-(5-(N-(3,4-dihydro-2-methyl-4-oxoquinazolin-6-ylmethyl)-N-methylamino)-2-thenoyl)L-glutamic acid
-
raltitrexed, no inhibition observed with the 5,10-dideazatetrahydrofolate resistant cells sublines
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
-
competitive with respect to MgATP2-
phosphate
-
competitive with respect to MgATP2-
phosphate
-
competitive with respect to MgATP2-
phosphate
-
-
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
methotrexate-phosphonate
-
IC50 0.00012 mM, at fixed substrate and recombinant enzyme concentrations
additional information
-
no inhibition by methotrexate in the CCRF-CEM R2 cell subline
-
additional information
-
in Escherichia coli, the addition of L-glutamate to dihydropteroate (dihydrofolate synthetase activity) and the subsequent additions of L-glutamate to tetrahydrofolate (folylpolyglutamate synthetase (FPGS) activity) are catalyzed by the same enzyme, FolC. The presence of a folate binding site in Escherichia coli FolC, which is different from the one seen in folylpolyglutamate synthetases, provides avenues for the design of specific inhibitors of this enzyme in antimicrobial therapy
-
additional information
-
no substrate: (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
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
2-mercaptoethanol
-
45 mM: 3.5fold enhancement of activity, 200 mM: 25% decrease in activity
2-mercaptoethanol
-
inhbibition above 100 mM; maximal stimulation at 25 mM
2-mercaptoethanol
-
maximal activity at 30-50 mM
3,3-difluoroglutamate
-
the incorporation of 3,3-difluoroglutamate promotes the further synthesis of polyglutamates
3,3-difluoroglutamate
-
i.e. beta,beta-difluoroglutamate??, , the effect on polyglutamylation is dependent on its position relative to the point of L-Glu ligation. When beta,beta-difluoroglutamate is the acceptor amino acid, i.e. point of attachment. Ligation of Glu is enhanced. When beta,beta-difluoroglutamate is one residue distal to the acceptor amino acid, further elongation is blocked
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
-
absolutely dependent on; beta-mercaptoethanol or DTT
-
Reducing agents
-
absolutely dependent on
-
Reducing agents
-
absolutely dependent on; beta-mercaptoethanol or DTT
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.002
(6R)-10-formyl-5,6,7,8-tetrahydropteroylglutamate
-
pH 8.9, 37C, L1210 isoform
0.0029
(6R)-10-formyl-5,6,7,8-tetrahydropteroylglutamate
-
pH 8.9, 37C, liver isoform
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
(6S)-5,6,7,8-tetrahydropteroylglutamate
-
pH 8.9, 37C, L1210 isoform
0.0063
(6S)-5,6,7,8-tetrahydropteroylglutamate
-
pH 8.9, 37C, liver isoform
0.075
(6S)-5-formyl-5,6,7,8-tetrahydropteroylglutamate
-
pH 8.9, 37C, L1210 isoform
0.122
(6S)-5-formyl-5,6,7,8-tetrahydropteroylglutamate
-
pH 8.9, 37C, liver isoform
0.054
(6S)-5-methylene-5,6,7,8-tetrahydropteroylglutamate
-
pH 8.9, 37C, L1210 isoform
0.064
(6S)-5-methylene-5,6,7,8-tetrahydropteroylglutamate
-
pH 8.9, 37C, liver isoform
0.0022
10-formyl-5,6,7,8-tetrahydropteroyl-Glu
-
-
0.0037
10-formyl-5,6,7,8-tetrahydropteroyl-Glu
-
-
0.0039
10-formyl-5,6,7,8-tetrahydropteroyl-Glu
-
-
0.014
10-formyl-5,6,7,8-tetrahydropteroyl-Glu
-
-
0.41
3,3-difluoroglutamate
-
reaction with methotrexate + ATP
0.0031
3,3-difluoromethotrexate
-
-
0.0054
3,3-difluoromethotrexate
-
-
0.0012
5,10-dideazatetrahydrofolic acid
-
pH 8.9, 37C, L1210 isoform
0.0076
5,10-dideazatetrahydrofolic acid
-
pH 8.9, 37C, liver isoform
0.03
5,10-methylene-5,6,7,8-tetrahydrofolic acid
-
pH 9.75
0.032
5,10-methylene-5,6,7,8-tetrahydrofolic acid
-
wild-type
0.034
5,10-methylene-5,6,7,8-tetrahydrofolic acid
-
mutant S152A, pH 9.8
0.048
5,10-methylene-5,6,7,8-tetrahydrofolic acid
-
mutant Y414A, pH 9.8
0.05
5,10-methylene-5,6,7,8-tetrahydrofolic acid
P08192
wild-type
0.071
5,10-methylene-5,6,7,8-tetrahydrofolic acid
P08192
chimera containing N-terminal residues 1-81 of Escherichia coli enzyme, residues 72-82 of Lactobacillus casei enzyme, and residues 93-422 of Escherichia coli enzyme, pH 9.8
0.071
5,10-methylene-5,6,7,8-tetrahydrofolic acid
-
chimera containing N-terminal residues 1-81 of Escherichia coli enzyme, residues 72-82 of Lactobacillus casei enzyme, and residues 93-422 of Escherichia coli enzyme, pH 9.8
0.084
5,10-methylene-5,6,7,8-tetrahydrofolic acid
-
mutant R15E, pH 9.8
0.11
5,10-methylene-5,6,7,8-tetrahydrofolic acid
-
mutant D151A, pH 9.8
0.116
5,10-methylene-5,6,7,8-tetrahydrofolic acid
-
mutant S152W, pH 9.8
0.118
5,10-methylene-5,6,7,8-tetrahydrofolic acid
P08192
chimera containing N-terminal residues 1-71 of Lactobacillus casei enzyme, residues 82-93 of Escherichia coli enzyme, and residues 83-428 of Lactobacillus casei enzyme, pH 9.8
0.118
5,10-methylene-5,6,7,8-tetrahydrofolic acid
-
chimera containing N-terminal residues 1-71 of Lactobacillus casei enzyme, residues 82-93 of Escherichia coli enzyme, and residues 83-428 of Lactobacillus casei enzyme, pH 9.8
0.23
5,10-methylene-5,6,7,8-tetrahydrofolic acid
-
mutant F75A, pH 9.8
0.59
5,10-methylene-5,6,7,8-tetrahydrofolic acid
P08192
chimera containing N-terminal residues 1-298 of Lactobacillus casei enzyme, residues 288-422 of Escherichia coli enzyme, pH 9.8
0.59
5,10-methylene-5,6,7,8-tetrahydrofolic acid
-
chimera containing N-terminal residues 1-298 of Lactobacillus casei enzyme, residues 288-422 of Escherichia coli enzyme, pH 9.8
1.5
5,10-methylene-5,6,7,8-tetrahydrofolic acid
-
mutant F121A, pH 9.8
3.8
5,10-methylene-5,6,7,8-tetrahydrofolic acid
-
mutant T119W, pH 9.8
0.01
5,10-methylene-5,6,7,8-tetrahydrofolyl-(L-Glu)2
-
mutant D151A, pH 9.8
0.204
5,10-methylene-5,6,7,8-tetrahydrofolyl-(L-Glu)2
-
mutant R15E, pH 9.8
0.0048
5,10-methylene-5,6,7,8-tetrahydropteroyl-Glu
-
-
0.027
5,10-methylene-5,6,7,8-tetrahydropteroyl-Glu
-
-
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
5,6,7,8-tetrahydrofolic acid
P08192
mutant A155W, pH 9.8
0.0315
5,6,7,8-tetrahydrofolic acid
-
pH 7.5, wild type enzyme
0.071
5,6,7,8-tetrahydrofolic acid
-
pH 7.5, E81A mutant
0.094
5,6,7,8-tetrahydrofolic acid
-
pH 7.5, S412A mutant
0.21
5,6,7,8-tetrahydrofolic acid
-
pH 7.5, R82A mutant
0.24
5,6,7,8-tetrahydrofolic acid
-
pH 7.5, K185A mutant
0.34
5,6,7,8-tetrahydrofolic acid
P08192
mutant D154A, pH 9.8
0.39
5,6,7,8-tetrahydrofolic acid
P08192
mutant T122W, pH 9.8
0.4
5,6,7,8-tetrahydrofolic acid
P08192
mutant T122H, pH 9.8
0.448
5,6,7,8-tetrahydrofolic acid
P08192
mutant A155H, pH 9.8
0.655
5,6,7,8-tetrahydrofolic acid
-
pH 7.5, S73A mutant
0.3
5,6,7,8-tetrahydrofolyl-gamma-(L-Glu)2
P08192
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
5,6,7,8-tetrahydropteroyl-Glu
-
-
0.0035
5,6,7,8-tetrahydropteroyl-Glu
-
-
0.0044
5,6,7,8-tetrahydropteroyl-Glu
-
aminopterin
0.006
5,6,7,8-tetrahydropteroyl-Glu
-
-
0.007
5,6,7,8-tetrahydropteroyl-Glu
-
-
0.0077
5,6,7,8-tetrahydropteroyl-Glu
-
-
0.009
5,6,7,8-tetrahydropteroyl-Glu
-
-
0.163
5,6,7,8-tetrahydropteroyl-Glu
-
-
0.336
5,6,7,8-tetrahydropteroyl-Glu
-
-
6.8
5,6,7,8-tetrahydropteroyl-Glu
-
-
0.0033
5,6,7,8-tetrahydropteroyl-Glu2
-
-
0.0034
5,6,7,8-tetrahydropteroyl-Glu2
-
-
0.0011
5,6,7,8-tetrahydropteroyl-Glu3
-
5,6,7,8-tetrahydropteroyl-Glu5
0.0014
5,6,7,8-tetrahydropteroyl-Glu3
-
-
0.0016
5,6,7,8-tetrahydropteroyl-Glu4
-
-
0.002
5,6,7,8-tetrahydropteroyl-Glu4
-
-
0.002
5,6,7,8-tetrahydropteroyl-Glu4
-
5,6,7,8-tetrahydropteroyl-Glu
0.002
5,6,7,8-tetrahydropteroyl-Glu4
-
7,8-dihydropteroyl-Glu
0.0027
5,6,7,8-tetrahydropteroyl-Glu5
-
-
0.0027
5,6,7,8-tetrahydropteroyl-Glu5
-
10-formyl-5,6,7,8-tetrahydropteroyl-Glu2
0.0081
5-formyl-5,6,7,8-tetrahydropteroyl-Glu
-
-
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
7,8-dihydropteroate
P08192
wild-type, pH 9.8
0.0063
7,8-dihydropteroate
-
wild-type, pH 9.8
0.08
7,8-dihydropteroate
P08192
mutant A155W, pH 9.8
0.134
7,8-dihydropteroate
P08192
chimera containing N-terminal residues 1-81 of Escherichia coli enzyme, residues 72-82 of Lactobacillus casei enzyme, and residues 93-422 of Escherichia coli enzyme, pH 9.8
0.134
7,8-dihydropteroate
-
chimera containing N-terminal residues 1-81 of Escherichia coli enzyme, residues 72-82 of Lactobacillus casei enzyme, and residues 93-422 of Escherichia coli enzyme, pH 9.8
0.14
7,8-dihydropteroate
P08192
mutant D154A, pH 9.8
0.15
7,8-dihydropteroate
P08192
mutant T122W, pH 9.8
0.485
7,8-dihydropteroate
P08192
mutant A155H, pH 9.8
0.98
7,8-dihydropteroate
P08192
mutant T122H, pH 9.8
0.012
7,8-dihydropteroyl-(4-aminobutanoyl)-Glu
-
-
0.012
7,8-dihydropteroyl-(4-aminobutanoyl)-Glu
-
pteroyl-Glu4
0.022
7,8-dihydropteroyl-(5-aminopentanoyl)-Glu
-
-
0.076
7,8-dihydropteroyl-beta-Ala-Glu
-
-
0.00081
7,8-dihydropteroyl-Glu
-
-
0.0009
7,8-dihydropteroyl-Glu
-
-
0.005
7,8-dihydropteroyl-Glu
-
-
0.0086
7,8-dihydropteroyl-Glu
-
-
0.0026
7,8-dihydropteroyl-Glu2
-
-
0.048
7,8-dihydropteroyl-Glu2
-
-
0.004
aminopterin
-
-
0.0043
aminopterin
-
-
0.0059
aminopterin
-
pH 8.9, 37C, HPLC assay, R377A mutant
0.0065
aminopterin
-
pH 8.9, 37C, HPLC assay, H338A mutant
0.009
aminopterin
-
pH 8.9, 37C, charcoal assay, wild type recombinant enzyme
0.0104
aminopterin
-
pH 8.7
0.011
aminopterin
-
pH 8.9, 37C, charcoal assay, K384A mutant
0.013
aminopterin
-
pH 8.9, 37C, charcoal assay, C346A mutant
0.0154
aminopterin
-
pH 8.9, 37C, L1210 isoform
0.017
aminopterin
-
-
0.017
aminopterin
-
pH 8.9, 37C, charcoal assay, D378A mutant
0.0177
aminopterin
-
pH 8.9, 37C, liver isoform
0.021
aminopterin
-
-
0.025
aminopterin
-
-
0.025
aminopterin
-
ATP
0.025
aminopterin
-
pteroyl-3,3-difluoroglutamate
0.031
aminopterin
-
pH 8.9, 37C, charcoal assay, D376A mutant
0.18
aminopterin
-
pH 8.9, 37C, HPLC assay, D335A mutant
0.0046
ATP
-
pH 8.9, 37C, HPLC assay, R377A mutant
0.01
ATP
-
reaction with 5,6,7,8-tetrahydropteroyl-Glu + ATP
0.01
ATP
-
ATP
0.01
ATP
-
5-formyl-5,6,7,8-tetrahydropteroyl-Glu
0.015
ATP
-
-
0.016
ATP
-
pH 8.9, 37C, HPLC assay, H338A mutant
0.028
ATP
-
pH 8.9, 37C, charcoal assay, D376A mutant
0.037
ATP
P08192
mutant D154A, pH 9.8 cosubstrate 7,8-dihydropteroate
0.04
ATP
-
pH 8.9, 37C, charcoal assay, C346A mutant
0.045
ATP
-
pH 8.9, 37C, charcoal assay, K384A mutant
0.046
ATP
-
pH 8.9, 37C, charcoal assay, wild type recombinant enzyme
0.046
ATP
-
pH 8.7
0.054
ATP
P08192
wild-type, pH 9.8
0.06
ATP
-
pH 8.9, 37C, charcoal assay, D378A mutant
0.065
ATP
P08192
mutant A155H, pH 9.8 cosubstrate 7,8-dihydropteroate
0.0665
ATP
-
reaction with 10-formyl-5,6,7,8-tetrahydropteroyl-Glu + Glu
0.07
ATP
-
pH 9.75, temperature conditions not mentioned
0.076
ATP
P08192
mutant A155H, pH 9.8, cosubstrate 5,6,7,8-tetrahydrofolic acid
0.18
ATP
-
mutant F75A, pH 9.8
0.23
ATP
P08192
mutant D154A, pH 9.8, cosubstrate 5,6,7,8-tetrahydrofolic acid
0.23
ATP
-
mutant Y414A, pH 9.8
0.25
ATP
-
reaction with aminopterin + ATP
0.267
ATP
-
pH 8.9, 37C, HPLC assay, D335A mutant
0.286
ATP
-
-
0.555
ATP
P08192
mutant A155W, pH 9.8 cosubstrate 7,8-dihydropteroate
0.62
ATP
-
pH 7.5, S412A mutant
0.87
ATP
-
pH 7.5, R82A mutant
2.3
ATP
-
-
2.5
ATP
-
pH 7.5, S73A mutant
2.9
ATP
-
pH 7.5, K185A mutant
3
ATP
-
pH 9.75
3.4
ATP
-
pH 7.5, wild type enzyme
3.4
ATP
-
mutant D151A, pH 9.8; wild-type, pH 9.8
5.2
ATP
-
pH 7.5, E81A mutant
5.7
ATP
P08192
chimera containing N-terminal residues 1-298 of Lactobacillus casei enzyme, residues 288-422 of Escherichia coli enzyme, pH 9.8
5.7
ATP
-
chimera containing N-terminal residues 1-298 of Lactobacillus casei enzyme, residues 288-422 of Escherichia coli enzyme, pH 9.8
35.7
ATP
-
-
0.05
dATP
-
reaction with 5,6,7,8-tetrahydropteroyl-Glu + ATP
0.0073
dihydroaminopterin
-
-
0.332
Glu
-
-
0.333
Glu
-
reaction with 10-formyl-5,6,7,8-tetrahydropteroyl-Glu
0.346
Glu
-
reaction with 5,6,7,8-tetrahydropteroyl-Glu + ATP
0.74
Glu
-
reaction with methotrexate + ATP
1.63
Glu
-
mutant enzyme A447V
1.702
Glu
-
wild type enzyme from cytosol
2.068
Glu
-
wild type enzyme from mitochondrion
2.281
Glu
-
mutant enzyme S457F
5.984
Glu
-
mutant enzyme R424C
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
L-Glu
-
mutant F75A, pH 9.8
0.12
L-Glu
P08192
mutant A155H, pH 9.8, cosubstrate 5,6,7,8-tetrahydrofolic acid
0.17
L-Glu
P08192
mutant A155H, pH 9.8, cosubstrate 7,8-dihydropteroate
0.2
L-Glu
-
MgATP2-
0.2
L-Glu
P08192
mutant D154A, pH 9.8, cosubstrate 5,6,7,8-tetrahydrofolic acid
0.292
L-Glu
P08192
chimera containing N-terminal residues 1-298 of Lactobacillus casei enzyme, residues 288-422 of Escherichia coli enzyme, pH 9.8
0.292
L-Glu
-
chimera containing N-terminal residues 1-298 of Lactobacillus casei enzyme, residues 288-422 of Escherichia coli enzyme, pH 9.8
0.3
L-Glu
P08192
wild-type, pH 9.8
0.423
L-Glu
-
-
0.47
L-Glu
-
wild-type, pH 9.8
0.61
L-Glu
-
-
0.82
L-Glu
-
-
1.2
L-Glu
-
reaction with aminopterin + ATP
2.7
L-Glu
-
mutant Y414A, pH 9.8
3.3
L-Glu
P08192
mutant D154A, pH 9.8, cosubstrate 5,6,7,8-tetrahydrofolic acid
150
L-Glu
-
-
0.24
L-glutamate
-
pH 8.7
0.41
L-glutamate
-
pH 7.5, E81A mutant
0.47
L-glutamate
-
pH 7.5, wild type enzyme
0.85
L-glutamate
-
pH 7.5, S73A mutant
1
L-glutamate
-
pH 8.5, 37C, wild type cell line
2 - 3
L-glutamate
-
pH 8.5, 37C, MTXR5 cell subline
2.06
L-glutamate
-
pH 7.5, R82A mutant
5.06
L-glutamate
-
pH 7.5, K185A mutant
26.69
L-glutamate
-
pH 7.5, S412A mutant
0.43
L-Glutamic acid
-
pH 8.9, 37C, charcoal assay, K384A mutant
0.52
L-Glutamic acid
-
pH 8.9, 37C, charcoal assay, C346A mutant
0.83
L-Glutamic acid
-
pH 8.9, 37C, charcoal assay, D378A mutant
2.9
L-Glutamic acid
-
pH 8.9, 37C, charcoal assay, D376A mutant
91
L-Glutamic acid
-
pH 8.9, 37C, HPLC assay, D335A mutant
140
L-Glutamic acid
-
pH 8.9, 37C, HPLC assay, H338A mutant
350
L-Glutamic acid
-
pH 8.9, 37C, HPLC assay, R377A mutant
0.019
methotrexate
-
-
0.04
methotrexate
-
pH 8.7
0.047
methotrexate
-
-
0.0526
methotrexate
-
wild type enzyme from mitochondrion
0.054
methotrexate
-
-
0.054
methotrexate
-
5-methyl-5,6,7,8-tetrahydrpteroyl-Glu
0.0555
methotrexate
-
wild type enzyme from cytosol
0.0613
methotrexate
-
mutant enzyme S457F
0.081
methotrexate
-
-
0.0827
methotrexate
-
mutant enzyme A447V
0.09
methotrexate
-
-
0.0908
methotrexate
-
mutant enzyme R424C
0.1
methotrexate
-
-
0.1
methotrexate
-
aminopterin
0.138
methotrexate
-
-
0.063
methotrexate-Glu
-
pH 8.5, 37C, wild type cell line
0.074
methotrexate-Glu
-
pH 8.5, 37C, MTXR5 cell subline
0.029
methotrexate-Glu2
-
-
0.02
methotrexate-Glu3
-
-
0.02
methotrexate-Glu3
-
pteroyl-Glu3
0.011
methotrexate-Glu4
-
methotrexate-Glu5
0.018
MgATP2-
-
ATP
0.018
MgATP2-
-
-
5.6
MgATP2-
-
-
0.126
N-(p(((2-amino-4-hydroxy-6-pteridinyl)methyl)-amino)benzoyl)glutamic acid
-
pH 8.7
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
pteroyl-Glu
-
-
0.06
pteroyl-Glu
-
-
0.115
pteroyl-Glu
-
-
0.132
pteroyl-Glu
-
-
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
-
pteroyl-Glu2
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
LITERATURE
IMAGE
0.095
(6R)-10-formyl-5,6,7,8-tetrahydropteroylglutamate
-
L1210 isoform
0.212
(6R)-10-formyl-5,6,7,8-tetrahydropteroylglutamate
-
liver isoform
0.116
(6S)-5,6,7,8-tetrahydropteroylglutamate
-
L1210 isoform
0.215
(6S)-5,6,7,8-tetrahydropteroylglutamate
-
liver isoform
0.073
(6S)-5-formyl-5,6,7,8-tetrahydropteroylglutamate
-
L1210 isoform
0.115
(6S)-5-formyl-5,6,7,8-tetrahydropteroylglutamate
-
liver isoform
0.01
5,10-dideazatetrahydrofolic acid
-
L1210 isoform
0.145
5,10-dideazatetrahydrofolic acid
-
liver isoform
0.99
5,6,7,8-tetrahydropteroyl-Glu
-
-
0.81
5,6,7,8-tetrahydropteroyl-Glu2
-
-
0.11
5-methyl-5,6,7,8-tetrahydropteroylglutamate
-
L1210 isoform
0.22
5-methyl-5,6,7,8-tetrahydropteroylglutamate
-
liver isoform
0.84
7,8-dihydropteroyl-Glu
-
-
0.95
7,8-dihydropteroyl-Glu2
-
-
0.165
aminopterin
-
L1210 isoform
0.22
aminopterin
-
liver isoform
1.17
aminopterin
-
-
2
aminopterin
-
-
0.65
pteroyl-Glu
-
-
0.82
pteroyl-Glu2
-
-
0.55
pteroyl-Glu3
-
-
0.34
pteroyl-Glu4
-
-
0.01
pteroyl-Glu5
-
-
1.7
L-Glu
-
-
additional information
additional information
-
-
-
additional information
additional information
-
-
-
additional information
additional information
-
-
-
additional information
additional information
-
-
-
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0023
(6R)-10-formyl-5,6,7,8-tetrahydropteroylpentaglutamate
-
Ki slope, L1210 isoform
0.0024
(6R)-10-formyl-5,6,7,8-tetrahydropteroylpentaglutamate
-
Ki slope, liver isoform
0.0042
(6R)-10-formyl-5,6,7,8-tetrahydropteroylpentaglutamate
-
Ki intercept, L1210 isoform
0.0052
(6R)-10-formyl-5,6,7,8-tetrahydropteroylpentaglutamate
-
Ki intercept, liver isoform
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
(6S)-5,10-methylene-5,6,7,8-tetrahydropteroylpentaglutamate
-
Ki slope, L1210 isoform
0.0083
(6S)-5,10-methylene-5,6,7,8-tetrahydropteroylpentaglutamate
-
Ki intercept, L1210 isoform
0.022
(6S)-5,10-methylene-5,6,7,8-tetrahydropteroylpentaglutamate
-
Ki slope, liver isoform
0.043
(6S)-5,10-methylene-5,6,7,8-tetrahydropteroylpentaglutamate
-
Ki intercept, liver isoform
0.0037
(6S)-5,6,7,8-tetrahydropteroylpentaglutamate
-
Ki slope, L1210 isoform
0.0083
(6S)-5,6,7,8-tetrahydropteroylpentaglutamate
-
Ki intercept, L1210 isoform
0.021
(6S)-5,6,7,8-tetrahydropteroylpentaglutamate
-
Ki slope, liver isoform
0.054
(6S)-5,6,7,8-tetrahydropteroylpentaglutamate
-
Ki intercept, liver isoform
0.066
(6S)-5-formyl-5,6,7,8-tetrahydropteroylpentaglutamate
-
Ki slope, L1210 isoform
0.084
(6S)-5-formyl-5,6,7,8-tetrahydropteroylpentaglutamate
-
Ki slope, liver isoform
0.02
(6S)-5-methyl-5,6,7,8-tetrahydropteroylpentaglutamate
-
Ki slope, L1210 isoform
0.055
(6S)-5-methyl-5,6,7,8-tetrahydropteroylpentaglutamate
-
Ki slope, liver isoform
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
methotrexate-phosphinate
-
Kis value, with methrotrexate as variable substrate, for recombinant enzyme
0.000056
methotrexate-phosphinate
-
Kii value, with methotrexate as variable substrate, for recombinant enzyme
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
LITERATURE
IMAGE
0.000008
(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
-
IC50 of 0.0000153 mM in the wild type cell line, IC50 of 0.000008 mM to 0.0016 mM in the antifolates-resistant sublines
0.0000635 - 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
-
IC50 of 0.0000125 mM in the wild type cell line, IC50 of 0.0000635 mM in the MTA-13 cell line
0.0000012
(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
0.000143
5,10-dideaza-5,6,7,8-tetrahydrofolic acid
-
IC50 of 0.0000277 mM in the wild type cell line, IC50 of 0.000143 mM to 0.0035 mM in the antifolates-resistant sublines
0.000205 - 13
5,10-dideaza-5,6,7,8-tetrahydrofolic acid
-
IC50 of 0.0000591 mM in the wild type cell line, IC50 of 0.000205 mM in the MTA-13 cell line
0.0000095
methotrexate
-
wild type enzyme from cytosol
0.0000129
methotrexate
-
mutant enzyme A447V
0.0000145
methotrexate
-
wild type enzyme from mitochondrion
0.0000156
methotrexate
-
mutant enzyme S457F
0.0000175
methotrexate
-
mutant enzyme R424C
0.000001
methotrexate-Glu
-
IC50 of 0.0000014 mM in the wild type cell line, IC50 of 0.000001 mM to 0.00095 mM in the antifolates-resistant sublines
0.0000545 - 13
methotrexate-Glu
-
IC50 of 0.00002 mM in the wild type cell line, IC50 of 0.0000545 mM in the MTA-13 cell line
0.000008
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
0.00012
methotrexate-phosphonate
-
IC50 0.00012 mM, at fixed substrate and recombinant enzyme concentrations
0.000028 - 13
N-(5-(N-(3,4-dihydro-2-methyl-4-oxoquinazolin-6-ylmethyl)-N-methylamino)-2-thenoyl)L-glutamic acid
-
IC50 of 0.0000033 mM in the wild type cell line, IC50 of 0.000028 mM in the MTA-13 cell line
0.00032
N-(5-(N-(3,4-dihydro-2-methyl-4-oxoquinazolin-6-ylmethyl)-N-methylamino)-2-thenoyl)L-glutamic acid
-
IC50 of 0.0000032 mM in the wild type cell line, IC50 of 0.00032 mM to 0.007168 mM in the antifolates-resistant sublines
0.000006
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
0.000011
pemetrexed
-
wild type enzyme from mitochondrion
0.0000127
pemetrexed
-
mutant enzyme A447V
0.0000136
pemetrexed
-
wild type enzyme from cytosol
0.0000263
pemetrexed
-
mutant enzyme R424C
0.0000302
pemetrexed
-
mutant enzyme S457F
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
-
-
additional information
2-[[[(4S)-4-carboxy-4-[(4-[[(2,4-diaminopteridin-6-yl)methyl](methyl)amino]benzoyl)amino]butyl](hydroxy)phosphoryl]methyl]pentanedioic acid
-
45 nM for species of low mobility, 3.5 nm for species of high mobility
additional information
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
-
51 nM for species of low mobility, 1.7 nM for species of high mobility
additional information
2-[[[(4S)-4-[(4-[[(2-amino-4-oxo-3,4-dihydropteridin-6-yl)methyl]amino]benzoyl)amino]-4-carboxybutyl](hydroxy)phosphoryl]methyl]pentanedioic acid
-
65 nM for species of low mobility, 6.5 nM for species of high mobility
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
-
IC50 of 0.0000136 mM in the wild type cell line, IC50 of 0.000116 mM in the MTA-13 cell line
additional information
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
-
576 nM for species of low mobility, 98 nM for species of high mobility
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
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
0.138
P08192
chimera containing N-terminal residues 1-81 of Escherichia coli enzyme, residues 72-82 of Lactobacillus casei enzyme, and residues 93-422 of Escherichia coli enzyme, substrate 5,10-methylene-5,6,7,8-tetrahydrofolic acid, pH 9.8
0.138
-
chimera containing N-terminal residues 1-81 of Escherichia coli enzyme, residues 72-82 of Lactobacillus casei enzyme, and residues 93-422 of Escherichia coli enzyme, substrate 5,10-methylene-5,6,7,8-tetrahydrofolic acid, pH 9.8
0.16
-
D345C mutant, pH 9.75
0.176
-
double mutant enzyme, pH 9.75
0.18
-
K172C mutant, pH 9.75
0.2
-
wild type enzyme, pH 9.75
0.2
-
wild type, pH 9.75
0.2
-
wild type enzyme
0.22
-
DEAE-Sephacel fraction
0.31
-
-
0.376
P08192
chimera containing N-terminal residues 1-81 of Escherichia coli enzyme, residues 72-82 of Lactobacillus casei enzyme, and residues 93-422 of Escherichia coli enzyme, substrate 7,8-dihydropteroate, pH 9.8
0.376
-
chimera containing N-terminal residues 1-81 of Escherichia coli enzyme, residues 72-82 of Lactobacillus casei enzyme, and residues 93-422 of Escherichia coli enzyme, substrate 7,8-dihydropteroate, pH 9.8
0.465
-
-
0.85
-
-
0.912
P08192
chimera containing N-terminal residues 1-71 of Lactobacillus casei enzyme, residues 82-93 of Escherichia coli enzyme, and residues 83-428 of Lactobacillus casei enzyme, substrate 5,10-methylene-5,6,7,8-tetrahydrofolic acid, pH 9.8
0.912
-
chimera containing N-terminal residues 1-71 of Lactobacillus casei enzyme, residues 82-93 of Escherichia coli enzyme, and residues 83-428 of Lactobacillus casei enzyme, substrate 5,10-methylene-5,6,7,8-tetrahydrofolic acid, pH 9.8
1.3
P08192
chimera containing N-terminal residues 1-298 of Lactobacillus casei enzyme, residues 288-422 of Escherichia coli enzyme, substrate 5,10-methylene-5,6,7,8-tetrahydrofolic acid, pH 9.8
1.3
-
chimera containing N-terminal residues 1-298 of Lactobacillus casei enzyme, residues 288-422 of Escherichia coli enzyme, substrate 5,10-methylene-5,6,7,8-tetrahydrofolic acid, pH 9.8
4.1
P08192
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
P08192
substrate 5,10-methylene-5,6,7,8-tetrahydrofolic acid, pH 9.8
45.6
-
-
additional information
-
-
additional information
-
-
additional information
-
-
additional information
-
-
additional information
-
-
additional information
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the specific activity of the extract derived from MTXR5 cell subline is 7.1fold lower than that obtained with the wild type cell line
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
8.2 - 8.4
-
-
8.2 - 9.5
-
-
8.4
-
glutamylation of methotrexate
9.4
-
-
9.6
-
-
pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
7 - 10
-
7.4: about 50% of maximal activity
7 - 10
-
7.4: about 50% of maximal activity; 7: about 20% of maximal activity, 10: about 50% of maximal activity
7.5 - 9
-
about 50% of maximal activity at pH 7.5 and 9
8 - 10
-
8: 20% of maximal activity, 9.5-10: maximal activity
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
37
-
assay at
TEMPERATURE RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
0 - 40
-
negligible activity at 0C and above 40C
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
-
leukemia line, wild type line and various antifolate-resistant sublines
Manually annotated by BRENDA team
-
T-lymphoblastic leukemia cell line
Manually annotated by BRENDA team
-
T-lymphoblastic leukemia line, wild type cell line and its methrotrexate transport-deficient subline R2
Manually annotated by BRENDA team
-
leukemic cells, cDNA, recombinant enzyme
Manually annotated by BRENDA team
-
the MTHFD1L transcript is detected at all stages of mouse embryogenesis examined
Manually annotated by BRENDA team
-
leukemia line
Manually annotated by BRENDA team
-
leukemia line, wild type and L7, L15, L44 and L51 5,10-dideazatetrahydrofolate resistant cells sublines
Manually annotated by BRENDA team
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leukemia line, wild type cell line and pemetrexed-resistant MTA-13 cell line
Manually annotated by BRENDA team
-
tumor, leukemic cells
Manually annotated by BRENDA team
-
acute nonlymphoblastic, K562 cell
Manually annotated by BRENDA team
-
there is a difference in the primary sequence of this isoform with respect to the leukemic cells isoform
Manually annotated by BRENDA team
-
FaDu cell line
Manually annotated by BRENDA team
-
A253 epidermoid carcinoma cell line
Manually annotated by BRENDA team
additional information
-
enzyme activity is at the limit of detection in intestine and lung and below detection in brain, heart, and skeletal muscle
Manually annotated by BRENDA team
additional information
-
the isozymes from the two tissues differ by 18 amino acids at their amino terminus
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
-
a single gene encodes both, mitochondrial and cytosolic isoforms of the enzyme
Manually annotated by BRENDA team
-
20% of the mycelial FPGS is mitochondrial
Manually annotated by BRENDA team
-
a single gene encodes both, mitochondrial and cytosolic isoforms of the enzyme
Manually annotated by BRENDA team
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mFGPS is at least in part strongly associated with the inner mitochondrial membrane
Manually annotated by BRENDA team
-
MTHFD1L enzyme is present and functional in mitochondria from normal embryonic tissues and embryonic fibroblast cell lines
Manually annotated by BRENDA team
additional information
-
distinct isoforms with different electrophoretic mobility
-
Manually annotated by BRENDA team
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
43000
-
gel filtration
1005, 1063
46000
-
gel filtration
1063
50900
-
predicted from amino acid sequence
671113
51000
-
gel filtration
1005, 1063, 1075, 1076, 1078
51000
-
SDS-PAGE
671113
60600
-
L1210 isoform
650131
61000
-
gel filtration
1089
62000
-
-
1092
62000
-
liver isoform
650131
65000
-
gel filtration
1081
65000
-
-
1097
66000
-
gel filtration
1063
68000
-
gel filtration
1082
68000
-
gel filtration
1093
68000
-
gel filtration
1094
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
?
-
x * 48000, SDS-PAGE
?
-
some anomalous behaviour in Sephadex G-150 suggests that the native or active form of the enzyme may be a multimer
?
-
x * 60128, SDS-PAGE
?
-
x * 60000, SDS-PAGE
?
-
x * 73000, SDS-PAGE
?
-
x * 66000, SDS-PAGE
monomer
-
-
monomer
-
1 * 62000, SDS-PAGE
monomer
-
1 * 53000, SDS-PAGE
monomer
-
1 * 43000, SDS-PAGE
monomer
-
1 * 47000, SDS-PAGE
monomer
-
1 * 61000, SDS-PAGE
monomer
-
1 * 68000, SDS-PAGE
monomer
-
1 * 51000, SDS-PAGE
Crystallization/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
hanging drop method in 1.2-1.7 M ammonium sulfate
-
enzyme-MgAMPPCP complex is produced by soaking apoFPGS crystals, grown overnight in a solution containing 20% PEG4000, 10 mM AMPPCP, 20 mM MgCl2, 100 mM KCl and 50 mM CAPSO, pH 9.0. The enzyme has a ATP-binding pocket in deep cleft formed between the N and C-domains, the folate-binding site is located in the interdomain cleft, His316, Ser412 and Lys346 are involved in the L-glutamate binding site
-
hanging drop vapour diffusion method using 50 mM acetate buffer pH 5.3 and 6% PEG 4000
-
microseeding, E143A mutant
-
batch method in the presence ADP and CoCl2 or vapour diffusion in the presence of ADP, dihydrofolate and CaCl2
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in complex with ADP and with adenylyl 5'-(beta,gamma-ethylene)diphosphonate at 2.0 and 2.3 A resolution, respectively. The nucleotide-binding site is deeply buried, while the binding of folate substrates occurs in a long extended groove. The active site beta5-alpha6-loop adopts an open position
O53174
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
37
-
t1/2: 8 min, in absence of ATP, t1/2: 38 min, stabilized by 5 mM ATP
1057
37
-
t1/2: 68 min, in absence of ATP
1057
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
K+ and phosphate stabilize
-
MgATP2-, ATP or sulfhydryl compounds increase the lability of the enzyme
-
2-mercaptoethanol enhances stabilization provided by ATP. ATP stabilizes against heat inactivation
-
the enzyme precipitates after a week at concentrations as low as 0.1 mg/ml
-
K+ and phosphate stabilize
-
stabilized by glycerol or by ATP
-
PMSF, benzamidine, and 20% v/v glycerol stabilize
-
50% glycerol stabilizes for several days at 4C
-
stability decreases markedly with further purification
-
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-20C, stable for 3 weeks
-
0C, in phosphate-mercaptoethanol, pH 7.5, 75% of activity is retained after 10 days, 55% after 3 weeks
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-20C or -196C, 50 mM potassium phosphate buffer, pH 7, 50 mM KCl, 30% DMSO
-
stable at 0-4C or at -20C
-
-20C, 0.05% n-octylglucoside, DTT 2 mM, 50% glycerol, stable for 9 months. Replenishment of DTT every 2 months is necesary.
-
-25C, 50% glycerol, stable
-
0-4C, stable for several days, or at -20C for longer periods
-
0C, leupeptin, MgATP2- 2 mM and 2-mercaptoethanol 50 mM or DTT 2 mM, limited stability. More stable with DTT in place of 2-mercaptoethanol.
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20C, Tris buffer, without thiols, 85% activity over 30 min.
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37C, Tris buffer, without thiols, with or without MgATP2- 5 mM, highly unstable, half-life of 6-7.3 min. Addition of 2-mercaptoethanol increases half-life of the enzyme to 11-21 min. Addition of 0.3 mg/ml BSA, stabilizes for 2 hours.
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-70C, 20% DMSO, stable
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-20C, buffered 50% glycerol, quite stable
-
partially stabilized in presence of glycerol
-
purified enzyme loses activity within 1-2 days at 4, without stabilizer
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Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
cytosolic, chloroplast and mitochondrial fractions
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partial
-
DE-52 cellulose column chromatography
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ammonium sulfate fractionation and chromatography on BioGel A-0.5M, recombinant enzyme
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ammonium sulfate fractionation, chromatography on Sephacryl S-100 and DEAE-Sephacel columns
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ammonium sulfate fractionation, chromatography on Sephacryl S-100HR and DEAE-Sephacel ion exchange column, 25fold purification
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crude total cell extracts are obtained by sonication followed by centrifugation
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partial purification
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chitin column chromatography
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chromatography on a chitin column
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ammonium sulfate precipitation, gel filtration and ion-exchange chromatography
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ammonium sulfate precipitation, Sephacryl S-100/HR and DEAE-Sephacel chromatography, recombinant enzymes
-
liver, partial
-
Ni-Sepharose 6 Fastflow resin chromatography and Superdex-200 gel filtration
-
differential centrifugation and ultracentrifugation on Nycodenz gradients, partial purification
-
two forms
-
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
expression in Saccharomyces cerevisiae FPGS deficient strains
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expression in Escherichia coli strain BL21
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high expression
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the folC gene from Escherichia coli is cloned into plasmid pET29. The resulting plasmid, pVRC1432, is transferred into the Escherichia coli BL21 strain
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expressed in AuxB1 cells
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expressed in Mus musculus
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expression in Escherichia coli
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expression in Escherichia coli FPGS deficient strain and in CHO AUXB1 cells
-
expression in Sf9 cells
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expression in Sf9 insect cells
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expression of wild type and mutant enzymes in Sf9 insect cells
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HCT-116 cells stable transfected with the sense or antisense FPGS cDNA. Compared with cells expressing endogenous FPGS, those overexpressing FPGS have significantly faster growth rates and higher concentrations of total folate and long-chain folate polyglutamates while antisense FPGS inhibition produces opposite results. FPGS overexpression significantly enhances, whereas FPGS inhibition decreases chemosensitivity to 5-fluorouracil. No significant difference in chemosensitivity to methotrexate is observed
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overexpression in Escherichia coli
-
expressed in Escherichia coli strain BL21
-
expression in Escherichia coli
-
expression in Escherichia coli strain BL21
-
expression in Sf9 insect cells
-
expression of the liver or L1210 isoforms in Sf9 insect cells
-
expression of wild type and mutant enzymes in AUXB1 cell line, which does not express measurable enzyme activity and is auxotrophic for the products of folate metabolism
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expressed in Escherichia coli strain BL21 (DELTADE3)
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expression in Escherichia coli
O53174
expression in Escherichia coli and Saccharomyces cerevisiae
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expression in Escherichia coli BL21 cells
-
overexpression in Escherichia coli
-
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
both TEL-AML1 and E2A-PBX1 down-regulate FPGS gene transcription through association with this multiprotein complex, and this complex also influences FPGS expression throughout lymphoblast cell cycle progression
-
correlation between expression and decrease in cell sensitivity
-
2- to 5fold increased mRNA expression after treatment with sodium butyrate or suberoylanilide hydroxamic acid
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expressed as single bifunctional protein with dihydrofolate synthase, EC 6.3.2.12
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ENGINEERING
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
A155H
P08192
drastic increases in Km values
A155W
P08192
13fold increase in Km value for dihydropteroate
D154A
P08192
mutation in residue specific for dihydropteroate binding, 200fold increase in Km value for substrate 5,6,7,8-tetrahydropteroyl-gamma-(L-Glu)2
T122H
P08192
drastic increases in Km values
T122W
P08192
drastic increases in Km values
A382T
-
94% of the wild type enzyme activity
A447V
-
does not affect enzyme activity
C209R
-
8% of the wild type enzyme activity
C346A
-
activity comparable with that of wild type enzyme
C346F
-
MTXR5 antifolates-resistant cell subline
D335A
-
with no significant activity
D376A
-
only slightly lower activity than the wild type enzyme
D378A
-
only slightly lower activity than the wild type enzyme
G569C
-
13% of the wild type enzyme activity
H338A
-
only 0.3% activity of the wild type enzyme
R377A
-
with no significant activity
R424C
-
reduced efficacy with substrates compared to the wild type enzyme
S457F
-
reduced efficacy with substrates compared to the wild type enzyme
D151A
-
mutation in residue specific for dihydropteroate binding, mutant is defective in using tetrahydrofolate as substrate
D313A
-
mutation in the C-terminal of the enzyme
D345C
-
more than 85% of the wild type activity, with 5,10-methylene-5,6,7,8-tetrahydrofolic acid as substrate
E143A
-
almost inactive
E143A
-
mutation in the MgATP2- binding site of the enzyme
E143D
-
almost inactive
E143D
-
mutation in the MgATP2- binding site of the enzyme
E143Q
-
almost inactive
E143Q
-
mutation in the MgATP2- binding site of the enzyme
E81A
-
mutation in the omega-loop of the enzyme
F121A
-
50fold increase in Km for 5,10-methylene-5,6,7,8-tetrahydrofolic acid
F75A
-
increase in Km value for 5,10-methylene-5,6,7,8-tetrahydrofolic acid, decreases in Km values for ATP and L-Glu
G411A
-
mutation in the C-terminal of the enzyme
G51S
-
no FGPS activity
G51S/S52T
-
no FGPS activity
H316A
-
mutation in the C-terminal of the enzyme
K172C
-
more than 85% of the wild type activity, with 5,10-methylene-5,6,7,8-tetrahydrofolic acid as substrate
P74A
-
mutation in the omega-loop of the enzyme
R15E
-
increases in Km values
R82A
-
mutation in the omega-loop of the enzyme
S152A
-
decrease in Vmax
S152W
-
increases in Km values
S412A
-
mutation in the C-terminal of the enzyme
S73A
-
mutation in the omega-loop of the enzyme
S73A
-
mutant retains some FGPS activity
T119W
-
100fold increase in Km for 5,10-methylene-5,6,7,8-tetrahydrofolic acid
Y414A
-
decrease in Km values for ATP, increase in Km for L-Glu
A337V
-
L44 cells
G178E
-
L7 cells
G320D
-
L15 cells
S180F
-
L51 cells
S67F
-
L51 cells, L7 cells
T339I
-
L44 cells
E146Q
-
completely inactive, no ATP binding is observed with this mutant
additional information
-
the enzyme cloned in a pUc19 vector is mutagenized by progressive deletion from both the 5'-end and the 3end and by TAB linker insertion. The specific activities of the extracts of the mutant enzyme are 4-16% that of the wild type enzyme. Non of the carboxy terminal or linker insertion mutants has a specific activity greater than 0.5% that of the wild type enzyme
additional information
P08192
expression of the amino-terminal domain with residues 1-287. The domain binds tetrahydrofolate and dihydropteroate with the same affinity as the intact enzyme. Construction of domain-swap chimera proteins between the Escherichia coli and the Lactobacillus casei enzymes. Chimera possess both folate or pteroate binding properties and enzymatic activities of their amino terminal portion, suggesting that the N-terminal domain determines the folate substrate specificity. Mutants with swapped omega loops, containing a folate binding site, retain the activities and folate or pteroate binding properties of the rest of the enzyme. Mutating Lactobacillus casei folypolyglutamate synthetase to contain an Escherichia coli folypolyglutamate synthetase dihydropteroate binding loop does not alter its substrate specificity to using dihydropteroate as a substrate
K384A
-
only slightly lower activity than the wild type enzyme
additional information
-
siRNA transfected into DLD-1 cells to downregulate folylpolyglutamate synthase reduces the basal level of reduced folate, the folate level after leucovorin treatment, and the enhancement of 5-fluoro-2'-deoxyuridine-induced cytotoxicity elicited by leucovorin. Folylpolyglutamate synthase and gamma-glutamyl hydrolase expression levels in tumors are determinants of the efficacy of leucovorin in enhancing the antitumor activity of 5-fluorouracil
K185A
-
mutation in the MgATP2- binding site of the enzyme
additional information
-
construction of domain-swap chimera proteins between the Escherichia coli and the Lactobacillus casei enzymes. Chimera possess both folate or pteroate binding properties and enzymatic activities of their amino terminal portion, suggesting that the N-terminal domain determines the folate substrate specificity. Mutants with swapped omega loops, containing a folate binding site, retain the activities and folate or pteroate binding properties of the rest of the enzyme. Mutating Lactobacillus casei folypolyglutamate synthetase to contain an Escherichia coli folypolyglutamate synthetase dihydropteroate binding loop does not alter its substrate specificity to using dihydropteroate as a substrate
W445stop
-
L15 cells
additional information
-
removal of the first 16 or 40 residues of the protein abolishes the enzyme activity in the yeast cell host, Saccharomyces cerevisiae but not in Escherichia coli
additional information
-
generation of methionine auxotrophs mutants by disruption of met7 gene, which encodes the enzyme
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
medicine
-
the enzyme inhibition can be useful for cancer chemotherapy
medicine
-
pemetrexed shows potent cytotoxicity in 211-H cells compared to A-549 cells and H-1299 cells, accompanied by significantly higher expression of foloylpolyglutamate synthase and reduced folate carrier 1. Simulltaneous exposure of pemtrexed and gemcitabine is antagonistic in all cell lines tested, while strong synergism is observed in 211-H cells when pemetrexed precedes gemcitabine
medicine
-
reduced folate carrier-1 and folylpolyglutamate synthase gene expression levels are significantly correlated in patients lacking p16 promoter hypermethylation in mucosa, but not at all correlated in patients having hypermethylation in mucosa. p16 Hypermethylation in mucosa of colorectal cancer patients is an independent prognostic parameter for cancer-specific survival as well as an independent predictor of disease-free survival
medicine
-
siRNA transfected into DLD-1 cells to downregulate folylpolyglutamate synthase reduces the basal level of reduced folate, the folate level after leucovorin treatment, and the enhancement of 5-fluoro-2'-deoxyuridine-induced cytotoxicity elicited by leucovorin. Folylpolyglutamate synthase and gamma-glutamyl hydrolase expression levels in tumors are determinants of the efficacy of leucovorin in enhancing the antitumor activity of 5-fluorouracil
analysis
-
assay procedure for the measurement of FPGS in up to 50 or 100 samples of partially purified enzyme at a time
medicine
-
target for antimalarial therapy