Information on EC 6.3.3.2 - 5-Formyltetrahydrofolate cyclo-ligase

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

EC NUMBER
COMMENTARY
6.3.3.2
-
RECOMMENDED NAME
GeneOntology No.
5-Formyltetrahydrofolate cyclo-ligase
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
ATP + 5-formyltetrahydrofolate = ADP + phosphate + 5,10-methenyltetrahydrofolate
show the reaction diagram
-
-
-
-
ATP + 5-formyltetrahydrofolate = ADP + phosphate + 5,10-methenyltetrahydrofolate
show the reaction diagram
sequential mechanism
-
ATP + 5-formyltetrahydrofolate = ADP + phosphate + 5,10-methenyltetrahydrofolate
show the reaction diagram
mechanism is proposed to involve phosphorylation of the formyl group to create an enol phosphate
-
ATP + 5-formyltetrahydrofolate = ADP + phosphate + 5,10-methenyltetrahydrofolate
show the reaction diagram
substrate binds to the enzyme by a random mechanism, Cleland-type mechanism
-
ATP + 5-formyltetrahydrofolate = ADP + phosphate + 5,10-methenyltetrahydrofolate
show the reaction diagram
random sequential mechanism
-
ATP + 5-formyltetrahydrofolate = ADP + phosphate + 5,10-methenyltetrahydrofolate
show the reaction diagram
mechanism involves phosphorylation of the formyl group at the N5-position, followed by displacement of the phosphate by the N10
-
ATP + 5-formyltetrahydrofolate = ADP + phosphate + 5,10-methenyltetrahydrofolate
show the reaction diagram
NMR analysis of the catalytic mechanism
-
ATP + 5-formyltetrahydrofolate = ADP + phosphate + 5,10-methenyltetrahydrofolate
show the reaction diagram
active site and substrate binding site structure
-
ATP + 5-formyltetrahydrofolate = ADP + phosphate + 5,10-methenyltetrahydrofolate
show the reaction diagram
active site and substrate binding site structure, binding and catalytic mechanism
-
REACTION TYPE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
heteroatomic ring closure
-
-
-
-
heteroatomic ring closure
-
-
heteroatomic ring closure
Q8L539
-
heteroatomic ring closure
-
-
heteroatomic ring closure
Q8LKF6, -
-
heteroatomic ring closure
-
-
PATHWAY
KEGG Link
MetaCyc Link
folate transformations I
-
folate transformations II
-
formylTHF biosynthesis
-
Metabolic pathways
-
One carbon pool by folate
-
SYSTEMATIC NAME
IUBMB Comments
5-Formyltetrahydrofolate cyclo-ligase (ADP-forming)
-
SYNONYMS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
5,10-methenyl-tetrahydrofolate synthetase
-
-
-
-
5,10-Methenyltetrahydrofolate synthetase
-
-
-
-
5,10-Methenyltetrahydrofolate synthetase
-
-
5,10-Methenyltetrahydrofolate synthetase
-
-
5,10-Methenyltetrahydrofolate synthetase
-
-
5,10-Methenyltetrahydrofolate synthetase
P49914
-
5,10-Methenyltetrahydrofolate synthetase
-
-
5,10-Methenyltetrahydrofolate synthetase
-
-
5,10-Methenyltetrahydrofolate synthetase
-
-
5,10-Methenyltetrahydropteroylglutamate synthetase
-
-
-
-
5-CHO-THF cycloligase
-
-
5-FCL
Q8L539
-
5-FCL
-
-
5-FCL
Q8LKF6
-
5-Formyltetrahydrofolate cyclodehydrase
-
-
-
-
CH+-THF synthetase
-
-
-
-
Formyltetrahydrofolic cyclodehydrase
-
-
-
-
Methenyl THFS
-
-
-
-
Methenyl-THF synthetase
-
-
-
-
Methenyltetrahydrofolate synthetase
-
-
-
-
Methenyltetrahydrofolate synthetase
-
-
Methenyltetrahydrofolate synthetase
-
-
Methenyltetrahydrofolate synthetase
-
-
Methenyltetrahydrofolate synthetase
-
-
MTHFS
-
-
-
-
MTHFS
P49914
-
N5-Formyltetrahydrofolic acid cyclodehydrase
-
-
-
-
Synthetase, methenyltetrahydrofolate
-
-
-
-
ygfA
E0IWA2
gene name
Methenyltetrahydrofolate synthetase
-
-
additional information
-
the enzyme belongs to the cycloligase protein family
CAS REGISTRY NUMBER
COMMENTARY
37318-64-2
-
GENERAL INFORMATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
malfunction
P49914
inhibition of MTHFS in human MCF-7 breast cancer cells arrests the growth of cells
metabolism
-
the enzyme is part of the folate-dependent one-carbon metabolism in the cytoplasm, overview
physiological function
P49914
MTHFS regulates the flow of carbon through the one-carbon metabolic network, which supplies essential components for the growth and proliferation of cells
physiological function
A0R3H2, -
mutant FUEL, which stands for folate utilization enzyme for leucovorin, is hypersusceptible to antifolates and unable to metabolize folinic acid. FUEL lacks 5,10-methenyltetrahydrofolate synthase MTHFS activity responsible for the only ATP-dependent, irreversible conversion of folinic acid to 5,10-methenyltetrahydrofolate. In trans expression of active MTHFS proteins from bacteria or human restores both antifolate resistance and folinic acid utilization to FUEL. Absence of MTHFS results in marked cellular accumulation of polyglutamylated species of folinic acid. MTHFS also affects Mycobacterium smegmatis utilization of monoglutamylated 5-methyltetrahydrofolate exogenously added to the medium
SUBSTRATE
PRODUCT                      
REACTION DIAGRAM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
araATP + 5-formyltetrahydrofolate
araADP + phosphate + 5,10-methylenetetrahydrofolate
show the reaction diagram
-
-
-
-
-
ATP + (6S)-5-formyltetrahydrofolate
ADP + 5,10-methenyltetrahydrofolate + phosphate
show the reaction diagram
-, Q9D110
-
-
-
?
ATP + 5-formyltetrahydrofolate
ADP + phosphate + 5,10-methylenetetrahydrofolate
show the reaction diagram
-
-
-
-
ATP + 5-formyltetrahydrofolate
ADP + phosphate + 5,10-methylenetetrahydrofolate
show the reaction diagram
-
-
-
-
ATP + 5-formyltetrahydrofolate
ADP + phosphate + 5,10-methylenetetrahydrofolate
show the reaction diagram
-
-
-
-
ATP + 5-formyltetrahydrofolate
ADP + phosphate + 5,10-methylenetetrahydrofolate
show the reaction diagram
-
-
-
-
ATP + 5-formyltetrahydrofolate
ADP + phosphate + 5,10-methylenetetrahydrofolate
show the reaction diagram
-
-
-
-
ATP + 5-formyltetrahydrofolate
ADP + phosphate + 5,10-methylenetetrahydrofolate
show the reaction diagram
-
-
-
-
ATP + 5-formyltetrahydrofolate
ADP + phosphate + 5,10-methylenetetrahydrofolate
show the reaction diagram
-
-
-
-
ATP + 5-formyltetrahydrofolate
ADP + phosphate + 5,10-methylenetetrahydrofolate
show the reaction diagram
-
-
-
-
ATP + 5-formyltetrahydrofolate
ADP + phosphate + 5,10-methylenetetrahydrofolate
show the reaction diagram
-
-
-
-
ATP + 5-formyltetrahydrofolate
ADP + phosphate + 5,10-methylenetetrahydrofolate
show the reaction diagram
-
-
-
-
ATP + 5-formyltetrahydrofolate
ADP + phosphate + 5,10-methylenetetrahydrofolate
show the reaction diagram
-
-
-
-
ATP + 5-formyltetrahydrofolate
ADP + phosphate + 5,10-methylenetetrahydrofolate
show the reaction diagram
-
-
-
-
ATP + 5-formyltetrahydrofolate
ADP + phosphate + 5,10-methylenetetrahydrofolate
show the reaction diagram
-
-
-
-
ATP + 5-formyltetrahydrofolate
ADP + phosphate + 5,10-methylenetetrahydrofolate
show the reaction diagram
-
-
-
-
ATP + 5-formyltetrahydrofolate
ADP + phosphate + 5,10-methylenetetrahydrofolate
show the reaction diagram
-
-
-
-
ATP + 5-formyltetrahydrofolate
ADP + phosphate + 5,10-methylenetetrahydrofolate
show the reaction diagram
-
-
-
-
ATP + 5-formyltetrahydrofolate
ADP + phosphate + 5,10-methylenetetrahydrofolate
show the reaction diagram
-
-
-
-
ATP + 5-formyltetrahydrofolate
ADP + phosphate + 5,10-methylenetetrahydrofolate
show the reaction diagram
Q8L539
-
-
ir
ATP + 5-formyltetrahydrofolate
ADP + phosphate + 5,10-methylenetetrahydrofolate
show the reaction diagram
-
no reverse reaction detected, (6R,S)-5-formyltetrahydrofolate, (6S)-5-formyltetrahydrofolate
-
-
ATP + 5-formyltetrahydrofolate
ADP + phosphate + 5,10-methylenetetrahydrofolate
show the reaction diagram
-
i.e. leucovorin, ir
-
-
ATP + 5-formyltetrahydrofolate
ADP + phosphate + 5,10-methylenetetrahydrofolate
show the reaction diagram
-
i.e. leucovorin, ir
-
-
ATP + 5-formyltetrahydrofolate
ADP + phosphate + 5,10-methenyltetrahydrofolate
show the reaction diagram
-
-
-
?
ATP + 5-formyltetrahydrofolate
ADP + phosphate + 5,10-methenyltetrahydrofolate
show the reaction diagram
-
-
-
-
?
ATP + 5-formyltetrahydrofolate
ADP + phosphate + 5,10-methenyltetrahydrofolate
show the reaction diagram
-
-
-
?, ir
ATP + 5-formyltetrahydrofolate
ADP + phosphate + 5,10-methenyltetrahydrofolate
show the reaction diagram
-
-
-
?
ATP + 5-formyltetrahydrofolate
ADP + phosphate + 5,10-methenyltetrahydrofolate
show the reaction diagram
-
-
-
?
ATP + 5-formyltetrahydrofolate
ADP + phosphate + 5,10-methenyltetrahydrofolate
show the reaction diagram
Q8L539
-
-
ir
ATP + 5-formyltetrahydrofolate
ADP + phosphate + 5,10-methenyltetrahydrofolate
show the reaction diagram
Q8LKF6, -
-
-
ir
ATP + 5-formyltetrahydrofolate
ADP + phosphate + 5,10-methenyltetrahydrofolate
show the reaction diagram
P49914
-
-
-
?
ATP + 5-formyltetrahydrofolate
ADP + phosphate + 5,10-methenyltetrahydrofolate
show the reaction diagram
-
enzyme prefers the polyglutamate forms of the substrate compared to the monoglutamate form
-
ir
ATP + 5-formyltetrahydrofolate
ADP + phosphate + 5,10-methenyltetrahydrofolate
show the reaction diagram
-
enzyme plays a central role in the regulation of folate-dependent, one-carbon metabolism
-
?
ATP + 5-formyltetrahydrofolate
ADP + phosphate + 5,10-methenyltetrahydrofolate
show the reaction diagram
-
enzyme plays an important role in one-carbon metabolism, overview about folate catabolism
-
ir
ATP + 5-formyltetrahydrofolate
ADP + phosphate + 5,10-methenyltetrahydrofolate
show the reaction diagram
P49914
folate binds in a spherical pocket, substrate binding and active site structure, structure-function analysis, detailed overview
-
-
?
ATP + 5-formyltetrahydrofolate
?
show the reaction diagram
-
-
-
-
-
ATP + 5-formyltetrahydrofolate
?
show the reaction diagram
-
key enzymatic reaction in the pathway by which 5-formyltetrahydrofolate enters the folate coenzyme pool
-
-
-
ATP + 5-formyltetrahydrofolate
?
show the reaction diagram
-
obligatory initial metabolic step in the intracellular conversion of 5-formyltetrahydrofolate to other reduced folates
-
-
-
ATP + 5-formyltetrahydrofolate
?
show the reaction diagram
-
it is proposed that methenyltetrahydrofolate synthetase is a salvage enzyme which converts the nonenzymatically formed and nonmetabolically active 5-formyltetrahydropteroyl-(Glu)n back into the one-carbon donor folate pool. It is also possible that methenyltetrahydrofolate synthetase is part of a regulation system in the cell in which its substrate 5-formyl-tetrahydropteroyl-(Glu)n plays a role as a regulator of one-carbon metabolism by inhibiting other folate requiring enzymes
-
-
-
ATP + 5-formyltetrahydrofolate
ADP + 5,10-methenyltetrahydrofolate + phosphate
show the reaction diagram
-
-
-
-
?
ATP + 5-formyltetrahydrofolate
ADP + 5,10-methenyltetrahydrofolate + phosphate
show the reaction diagram
-
-
-
-
ir
ATP + 5-formyltetrahydrofolate
ADP + 5,10-methenyltetrahydrofolate + phosphate
show the reaction diagram
-
-
-
-
?
ATP + 5-formyltetrahydrofolate
ADP + 5,10-methenyltetrahydrofolate + phosphate
show the reaction diagram
-
-
-
-
?
ATP + 5-formyltetrahydrofolate
ADP + 5,10-methenyltetrahydrofolate + phosphate
show the reaction diagram
-
-
-
-
?
ATP + 5-formyltetrahydrofolate
ADP + 5,10-methenyltetrahydrofolate + phosphate
show the reaction diagram
-
-
-
-
?
ATP + 5-formyltetrahydrofolate
ADP + 5,10-methenyltetrahydrofolate + phosphate
show the reaction diagram
-
-
-
-
?
ATP + 5-formyltetrahydrofolate
ADP + 5,10-methenyltetrahydrofolate + phosphate
show the reaction diagram
P75430
-
-
-
?
ATP + 5-formyltetrahydrofolate
ADP + 5,10-methenyltetrahydrofolate + phosphate
show the reaction diagram
-, Q81LX0
-
-
-
?
ATP + 5-formyltetrahydrofolate
ADP + 5,10-methenyltetrahydrofolate + phosphate
show the reaction diagram
-
important reaction in one-carbon donor recycling
-
-
?
ATP + 5-formyltetrahydrofolate
ADP + 5,10-methenyltetrahydrofolate + phosphate
show the reaction diagram
-
recycling reaction
-
-
?
ATP + 5-formyltetrahydrofolate
ADP + 5,10-methenyltetrahydrofolate + phosphate
show the reaction diagram
-, Q9D110
the enzyme affects intracellular folate concentrations by accelerating folate degradation
-
-
?
ATP + 5-formyltetrahydrofolate
ADP + 5,10-methenyltetrahydrofolate + phosphate
show the reaction diagram
-
i.e. 5-FTHF or leucovirin
-
-
?
ATP + 5-formyltetrahydrofolate-pentaglutamate
ADP + phosphate + 5,10-methylenetetrahydrofolate-pentaglutamate
show the reaction diagram
Q8L539
preferred substrate to the monoglutamyl form
-
ir
ATP + 5-formyltetrahydrohomofolate
?
show the reaction diagram
-
-
-
-
-
ATP + 5-formyltetrahydropteroyl-pentaglutamate
?
show the reaction diagram
-
-
-
-
-
ATP + 5-formyltetrahydropteroyl-pentaglutamate
?
show the reaction diagram
-
-
-
-
-
ATPgammaS + 5-formyltetrahydrofolate
ADPgammaS + phosphate + 5,10-methylenetetrahydrofolate
show the reaction diagram
-
-
-
-
-
CTP + 5-formyltetrahydrofolate
CDP + phosphate + 5,10-methylenetetrahydrofolate
show the reaction diagram
-
-
-
-
-
CTP + 5-formyltetrahydrofolate
CDP + phosphate + 5,10-methylenetetrahydrofolate
show the reaction diagram
-
-
-
-
-
CTP + 5-formyltetrahydrofolate
CDP + phosphate + 5,10-methylenetetrahydrofolate
show the reaction diagram
-
as effective as ATP
-
-
-
dATP + 5-formyltetrahydrofolate
dADP + phosphate + 5,10-methylenetetrahydrofolate
show the reaction diagram
-
-
-
-
-
dTTP + 5-formyltetrahydrofolate
dTDP + phosphate + 5,10-methylenetetrahydrofolate
show the reaction diagram
-
-
-
-
-
GTP + 5-formyltetrahydrofolate
GDP + phosphate + 5,10-methylenetetrahydrofolate
show the reaction diagram
-
-
-
-
-
GTP + 5-formyltetrahydrofolate
GDP + phosphate + 5,10-methylenetetrahydrofolate
show the reaction diagram
-
-
-
-
-
UTP + 5-formyltetrahydrofolate
UDP + phosphate + 5,10-methylenetetrahydrofolate
show the reaction diagram
-
-
-
-
-
UTP + 5-formyltetrahydrofolate
UDP + phosphate + 5,10-methylenetetrahydrofolate
show the reaction diagram
-
-
-
-
-
ITP + 5-formyltetrahydrofolate
IDP + phosphate + 5,10-methylenetetrahydrofolate
show the reaction diagram
-
-
-
-
-
additional information
?
-
Q8L539
enzyme is specific for the 6S-isomer
-
?
additional information
?
-
-, Q9D110
disruption of folate metabolism is associated with several pathologies and developmental anomalies including cancer and neural tube defects
-
-
-
additional information
?
-
-
5-formyltetrahydrohomofolate, 10-formyltetrahydrohomofolate, and 5-formyl,10-methyltetrahydrofolate are no substrates
-
-
-
additional information
?
-
-
increased MTHFS expression affects the efficacy of the glycinamide ribonucleotide formyltransferase inhibitor LY309887, overview. SH-SY5Y neuroblastoma with increased MTHFS expression display a 4fold resistance to the GARFT inhibitor LY309887, but do not exhibit resistance to the thymidylate synthase inhibitor Pemetrexed.
-
-
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
ATP + 5-formyltetrahydrofolate
ADP + phosphate + 5,10-methenyltetrahydrofolate
show the reaction diagram
-
-
-
?
ATP + 5-formyltetrahydrofolate
ADP + phosphate + 5,10-methenyltetrahydrofolate
show the reaction diagram
-
-
-
-
?
ATP + 5-formyltetrahydrofolate
ADP + phosphate + 5,10-methenyltetrahydrofolate
show the reaction diagram
-
-
-
?
ATP + 5-formyltetrahydrofolate
ADP + phosphate + 5,10-methenyltetrahydrofolate
show the reaction diagram
-
-
-
?
ATP + 5-formyltetrahydrofolate
ADP + phosphate + 5,10-methenyltetrahydrofolate
show the reaction diagram
Q8L539
-
-
ir
ATP + 5-formyltetrahydrofolate
ADP + phosphate + 5,10-methenyltetrahydrofolate
show the reaction diagram
Q8LKF6, -
-
-
ir
ATP + 5-formyltetrahydrofolate
ADP + phosphate + 5,10-methenyltetrahydrofolate
show the reaction diagram
P49914
-
-
-
?
ATP + 5-formyltetrahydrofolate
ADP + phosphate + 5,10-methenyltetrahydrofolate
show the reaction diagram
-
enzyme plays a central role in the regulation of folate-dependent, one-carbon metabolism
-
?
ATP + 5-formyltetrahydrofolate
ADP + phosphate + 5,10-methenyltetrahydrofolate
show the reaction diagram
-
enzyme plays an important role in one-carbon metabolism, overview about folate catabolism
-
ir
ATP + 5-formyltetrahydrofolate
?
show the reaction diagram
-
-
-
-
-
ATP + 5-formyltetrahydrofolate
?
show the reaction diagram
-
key enzymatic reaction in the pathway by which 5-formyltetrahydrofolate enters the folate coenzyme pool
-
-
-
ATP + 5-formyltetrahydrofolate
?
show the reaction diagram
-
obligatory initial metabolic step in the intracellular conversion of 5-formyltetrahydrofolate to other reduced folates
-
-
-
ATP + 5-formyltetrahydrofolate
?
show the reaction diagram
-
it is proposed that methenyltetrahydrofolate synthetase is a salvage enzyme which converts the nonenzymatically formed and nonmetabolically active 5-formyltetrahydropteroyl-(Glu)n back into the one-carbon donor folate pool. It is also possible that methenyltetrahydrofolate synthetase is part of a regulation system in the cell in which its substrate 5-formyl-tetrahydropteroyl-(Glu)n plays a role as a regulator of one-carbon metabolism by inhibiting other folate requiring enzymes
-
-
-
ATP + 5-formyltetrahydrofolate
ADP + 5,10-methenyltetrahydrofolate + phosphate
show the reaction diagram
-
-
-
-
?
ATP + 5-formyltetrahydrofolate
ADP + 5,10-methenyltetrahydrofolate + phosphate
show the reaction diagram
-
important reaction in one-carbon donor recycling
-
-
?
ATP + 5-formyltetrahydrofolate
ADP + 5,10-methenyltetrahydrofolate + phosphate
show the reaction diagram
-
recycling reaction
-
-
?
ATP + 5-formyltetrahydrofolate
ADP + 5,10-methenyltetrahydrofolate + phosphate
show the reaction diagram
-, Q9D110
the enzyme affects intracellular folate concentrations by accelerating folate degradation
-
-
?
additional information
?
-
-, Q9D110
disruption of folate metabolism is associated with several pathologies and developmental anomalies including cancer and neural tube defects
-
-
-
additional information
?
-
-
increased MTHFS expression affects the efficacy of the glycinamide ribonucleotide formyltransferase inhibitor LY309887, overview. SH-SY5Y neuroblastoma with increased MTHFS expression display a 4fold resistance to the GARFT inhibitor LY309887, but do not exhibit resistance to the thymidylate synthase inhibitor Pemetrexed.
-
-
-
COFACTOR
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
ATP
Q8L539
dependent on
ATP
-
dependent on
ATP
Q8LKF6, -
dependent on
ATP
-, Q9D110
dependent on, as MgATP2-, binding site motifs
ATP
-
absolutely required, as MgATP2-, binding structure
MgATP2-
-
enzyme is inhibited by salt, therefore MgATP2- is used as cofactor instead of MgCl2 and NaATP-
additional information
-
no activity with nucleoside 5'-mono- or 5'-diphosphates
-
METALS and IONS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
Ca2+
-
as effective as Mg2+
Ca2+
-
can replace Mg2+
Ca2+
-
activates, can substitute for Mg2+
Co2+
-
slightly more effective than Mg2+
Co2+
-
as effective as Mg2+
Co2+
-
can replace Mg2+
Co2+
-
activates, can substitute for Mg2+
Cu2+
-
activates, can substitute for Mg2+
Fe2+
-
activates, can substitute for Mg2+
Mg2+
-
required
Mg2+
-
required
Mg2+
-
no divalent metal ion dependence beyond that required in the MgATP2- substrate complex
Mg2+
-
required
Mg2+
-
required in equivalent concentration with ATP, its only role is to form a complex with ATP
Mg2+
-
-
Mg2+
-, Q9D110
as MgATP2-
Mg2+
-
dependent on, most effective divalent cation, required for MgATP2- complex formation, binding structure
Mg2+
-, Q81LX0
dependent
Mg2+
-
dependent
Mn2+
-
as effective as Mg2+
Zn2+
-
activates, can substitute for Mg2+
Mn2+
-
activates, can substitute for Mg2+
additional information
-
the enzyme is dependent on divalent cation, Mg2+ is preferred
INHIBITORS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
10-formylfolic acid
-
-
4-Amino-N10-methylpteroyl pentaglutamate
-
i.e. methotrexate pentaglutamate
5-formyl,10-methyltetrahydrofolate
-
weak inhibitor
5-Formyltetrahydrohomofolate
-
most potent inhibitor
5-Formyltetrahydrohomofolate
-
-
5-Formyltetrahydrohomofolate
-
effective inhibitor
5-methyltetrahydrofolate
-
-
5-methyltetrahydrofolate
-
competitive with respect to 5-formyltetrahydrofolate
dihydropteroyl pentaglutamate
-
potent
dihydropteroyl-L-Glu
-
weak
folic acid
-
-
folic acid pentaglutamate
-
-
-
folic acid triglutamate
-
-
lometrexol
-
competitive inhibition of murine MTHFS in vitro
LY309887
-
competitive inhibition of murine MTHFS in vitro
Maleate
-
-
-
N-(4-{[2-(2-amino-5-formyl-4-oxo-1,4,5,6,7,8-hexahydropteridin-6-yl)ethyl](methyl)amino}benzoyl)-L-glutamic acid
-
at 37C in 100 mM MES, pH 6.0
o-Iodosobenzoate
-
-
p-mercuribenzoate
-
-
pemetrexed
-
competitive inhibition of murine MTHFS in vitro
phosphate
-
product inhibition
[6R,S]-10-formyltetrahydrofolate triglutamate
-
-
[6R,S]-10-formyltetrahydrohomofolate
-
-
[6R,S]-10-formyltetrahydropteroate
-
-
[6R,S]-5-formyl,10-methyltetrahydrofolateGlu3
-
-
[6R,S]-5-formyl,11-methyltetrahydrohomofolate
-
-
[6R,S]-5-formyltetrahydrohomofolate
-
-
[6R]-10-formyltetrahydrofolate
-
-
[6R]-10-formyltetrahydrofolate
-
-
additional information
-
no inhibition by methotrexate
-
additional information
-
enzyme is inhibited by salt, therefore MgATP2- is used as cofactor instead of MgCl2 and NaATP-
-
additional information
-
inhibition mechanism overview
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
5-formyltetrahydrofolate polyglutamate
-
induced recombinant enzyme expression in cancer cell cultures, increasing effect with increasing chain length
N-acetyldopamine
-
0.02 mM, accelerates markedly folate turnover
dopamine
-
0.02 mM, increases the initial rapid phase of folate turnover by 4%
additional information
-
L-dopa does not affect folate turnover rate
-
KM VALUE [mM]
KM VALUE [mM] Maximum
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.004
-
(6R,S)-5-formyltetrahydrofolate
-
-
0.0044
-
(6R,S)-5-formyltetrahydropteroyl-Glu
-
cytosolic enzyme
0.0047
-
(6R,S)-5-formyltetrahydropteroyl-Glu
-
mitochondrial enzyme
0.0047
-
(6R,S)-5-formyltetrahydropteroyl-Glu
-
-
0.002
-
(6S)-5-formyltetrahydrofolate
-
-
0.005
-
(6S)-5-formyltetrahydrofolate
-, Q9D110
pH 6.0, 28C, recombinant enzyme
0.0008
-
(6S)-5-formyltetrahydropteroyl pentaglutamate
-
mitochondrial enzyme
0.0006
-
(6S)-5-formyltetrahydropteroyl-pentaglutamate
-
-
0.0006
-
(6S)-5-formyltetrahydropteroyl-pentaglutamate
-
cytosolic enzyme
0.0002
-
5-formyl-tetrahydropteroyl-pentaglutamate
-
-
0.0005
-
5-formyltetrahydrofolate
-
-
0.0006
-
5-formyltetrahydrofolate
-
-
0.0025
-
5-formyltetrahydrofolate
-, P75430
wild type enzyme, in 200 mM MES pH 6.0, with 30 mM NaCl, 10 mM MgCl2, 0.1% (v/v) Triton X-100, and 0.01% (v/v) 2-mercaptoethanol, at 37C
0.0051
-
5-formyltetrahydrofolate
-
-
0.0071
-
5-formyltetrahydrofolate
-, P75430
mutant enzyme K120A, in 200 mM MES pH 6.0, with 30 mM NaCl, 10 mM MgCl2, 0.1% (v/v) Triton X-100, and 0.01% (v/v) 2-mercaptoethanol, at 37C
0.008
-
5-formyltetrahydrofolate
-
-
0.009
-
5-formyltetrahydrofolate
-
mutant enzyme Y151A, in 100 mM MES, pH 6.0, at 37C
0.01
-
5-formyltetrahydrofolate
-
wild type enzyme, in 100 mM MES, pH 6.0, at 37C
0.033
-
5-formyltetrahydrofolate
-
recombinant enzyme, pH 7.0, 30C
0.047
-
5-formyltetrahydrofolate
-
mutant enzyme Y152F, in 100 mM MES, pH 6.0, at 37C
0.14
-
5-formyltetrahydrofolate
-
-
0.165
-
5-formyltetrahydrofolate
-
pH 6.0, 37C, recombinant enzyme
3
-
5-formyltetrahydrofolate
-
mutant enzyme Y152A, in 100 mM MES, pH 6.0, at 37C
0.0056
-
araATP
-
-
0.00096
-
ATP
-
-
0.02
-
ATP
-
cytosolic enzyme
0.022
-
ATP
-
mitochondrial enzyme
0.022
-
ATP
-
-
0.043
-
ATP
-
recombinant enzyme, pH 7.0, 30C
0.076
-
ATP
-, P75430
wild type enzyme, in 200 mM MES pH 6.0, with 30 mM NaCl, 10 mM MgCl2, 0.1% (v/v) Triton X-100, and 0.01% (v/v) 2-mercaptoethanol, at 37C
0.45
-
ATP
-
-
1.2
-
ATP
-, P75430
mutant enzyme K120A, in 200 mM MES pH 6.0, with 30 mM NaCl, 10 mM MgCl2, 0.1% (v/v) Triton X-100, and 0.01% (v/v) 2-mercaptoethanol, at 37C
0.00021
-
ATPgammaS
-
-
0.0016
-
CTP
-
-
0.0013
-
dATP
-
-
0.0066
-
dTTP
-
-
0.0003
-
MgATP2-
-
-
0.001
-
MgATP2-
-
-
0.166
-
MgATP2-
-
pH 6.0, 37C, recombinant enzyme
0.3
-
MgATP2-
-
Km-value is constant over the pH-range 5.0-7.5
0.3
-
MgATP2-
-
-
0.769
-
MgATP2-
-, Q9D110
recombinant enzyme
0.4
-
MgCTP2-
-
-
0.6
-
MgCTP2-
-
-
0.0064
-
UTP
-
-
0.5
-
MgUTP2-
-
-
additional information
-
additional information
-
kinetics
-
additional information
-
additional information
-
steady-state kinetics, recombinant enzyme
-
TURNOVER NUMBER [1/s]
TURNOVER NUMBER MAXIMUM[1/s]
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
16.3
-
(6S)-5-formyltetrahydrofolate
-, Q9D110
pH 6.0, 28C, recombinant enzyme
0.02
-
5-formyltetrahydrofolate
-
mutant enzyme Y152A, in 100 mM MES, pH 6.0, at 37C
0.79
-
5-formyltetrahydrofolate
-, P75430
wild type enzyme, in 200 mM MES pH 6.0, with 30 mM NaCl, 10 mM MgCl2, 0.1% (v/v) Triton X-100, and 0.01% (v/v) 2-mercaptoethanol, at 37C
0.92
-
5-formyltetrahydrofolate
-
mutant enzyme Y151A, in 100 mM MES, pH 6.0, at 37C
0.94
-
5-formyltetrahydrofolate
-
pH 6.0, 37C, recombinant enzyme
1.3
-
5-formyltetrahydrofolate
-, P75430
mutant enzyme K120A, in 200 mM MES pH 6.0, with 30 mM NaCl, 10 mM MgCl2, 0.1% (v/v) Triton X-100, and 0.01% (v/v) 2-mercaptoethanol, at 37C
3.33
-
5-formyltetrahydrofolate
-
wild type enzyme, in 100 mM MES, pH 6.0, at 37C
4.3
-
5-formyltetrahydrofolate
-
mutant enzyme Y152F, in 100 mM MES, pH 6.0, at 37C
5.3
-
5-formyltetrahydrofolate
Q8L539
truncated recombinant enzyme, pH 6.0, 23C
1
-
ATP
-, P75430
wild type enzyme, in 200 mM MES pH 6.0, with 30 mM NaCl, 10 mM MgCl2, 0.1% (v/v) Triton X-100, and 0.01% (v/v) 2-mercaptoethanol, at 37C
1.7
-
ATP
-, P75430
mutant enzyme K120A, in 200 mM MES pH 6.0, with 30 mM NaCl, 10 mM MgCl2, 0.1% (v/v) Triton X-100, and 0.01% (v/v) 2-mercaptoethanol, at 37C
0.99
-
MgATP2-
-
pH 6.0, 37C, recombinant enzyme
additional information
-
additional information
-
-
-
additional information
-
additional information
-
-
-
additional information
-
additional information
-
-
-
Ki VALUE [mM]
Ki VALUE [mM] Maximum
INHIBITOR
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.013
-
10-formylfolic acid
-
at 37C in 100 mM MES, pH 6.0
0.001
-
5-formyl,10-methyltetrahydrofolate
-
at 37C in 100 mM MES, pH 6.0
0.0007
-
5-Formyltetrahydrohomofolate
-
at 37C in 100 mM MES, pH 6.0
0.058
-
folic acid
-
at 37C in 100 mM MES, pH 6.0
0.0001
-
folic acid pentaglutamate
-
at 37C in 100 mM MES, pH 6.0
-
0.0017
-
folic acid triglutamate
-
at 37C in 100 mM MES, pH 6.0
0.009
-
lometrexol
-
-
0.006
-
LY309887
-
-
0.048
-
pemetrexed
-
-
2.12
-
phosphate
-
pH 6.0, 37C, recombinant enzyme
3e-05
-
[6R,S]-10-formyltetrahydrofolate triglutamate
-
at 37C in 100 mM MES, pH 6.0
0.0002
-
[6R,S]-10-formyltetrahydrohomofolate
-
at 37C in 100 mM MES, pH 6.0
0.005
-
[6R,S]-10-formyltetrahydropteroate
-
at 37C in 100 mM MES, pH 6.0
0.02
-
[6R,S]-5-formyl,10-methyltetrahydrofolateGlu3
-
at 37C in 100 mM MES, pH 6.0
0.006
-
[6R,S]-5-formyl,11-methyltetrahydrohomofolate
-
at 37C in 100 mM MES, pH 6.0
0.0007
-
[6R,S]-5-formyltetrahydrohomofolate
-
at 37C in 100 mM MES, pH 6.0
0.00015
-
[6R]-10-formyltetrahydrofolate
-
at 37C in 100 mM MES, pH 6.0
0.00015
-
[6R]-10-formyltetrahydrofolate
-
-
IC50 VALUE [mM]
IC50 VALUE [mM] Maximum
INHIBITOR
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.223
-
lometrexol
-
recombinant SH-SY5Y cells overexpressing MTHFS
0.303
-
lometrexol
-
wild-type SH-SY5Y cells
0.014
-
LY309887
-
wild-type SH-SY5Y cells
0.029
-
LY309887
-
recombinant SH-SY5Y cells overexpressing MTHFS
0.033
-
pemetrexed
-
wild-type SH-SY5Y cells
0.045
-
pemetrexed
-
recombinant SH-SY5Y cells overexpressing MTHFS
SPECIFIC ACTIVITY [µmol/min/mg]
SPECIFIC ACTIVITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
6e-05
-
-
placenta
0.00026
-
-
postweaning, brain
0.00032
-
-
kidney
0.00036
-
-
fetal liver
0.0011
-
-
adult liver
0.0015
-
-
3 weeks old liver
2.22
-
-, Q9D110
purified recombinant enzyme
2.8
-
-
purified recombinant enzyme
7
-
-
purified recombinant enzyme
37
-
-
-
additional information
-
-
-
additional information
-
-
-
additional information
-
-
activity in disruption mutant strains
additional information
-
Q8L539
activity of recombinant enzyme lacking the mitochondrial targeting sequence is significantly higher than the activity of the full length recombinant enzyme
additional information
-
Q8LKF6, -
activity of recombinant enzyme lacking the mitochondrial targeting sequence is significantly higher than the activity of the full length recombinant enzyme
additional information
-
-
activity of recombinantly expressed enzyme in different cell cultures
pH OPTIMUM
pH MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
4.8
-
-
-
6
-
-
assay at
6
-
-, Q9D110
assay at
6
-
-
assay at
6.5
-
-
cytosolic enzyme
6.5
-
-
assay at
7.4
-
-
assay at
8.5
-
Q8L539
bicine buffer
pH RANGE
pH RANGE MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
4
6
-
4.0: about 50% of maximal activity, 6.0: about 60% of maximal activity
5.5
9
Q8L539
linear increase of activity to maximum at pH 8.5
TEMPERATURE OPTIMUM
TEMPERATURE OPTIMUM MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
24
28
-, Q9D110
assay at
30
-
-
assay at
30
-
-
assay at
37
-
-
assay at
37
-
-
assay at
SOURCE TISSUE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
SOURCE
-
low activity
Manually annotated by BRENDA team
-
increase during development
Manually annotated by BRENDA team
-
low enzyme expression
Manually annotated by BRENDA team
-
T-lymphoblast cell line CEM and its methotrexate resistant subline, colon tumor cell line
Manually annotated by BRENDA team
-
CHO, ovary cell line and its methotrexate resistant subline
Manually annotated by BRENDA team
-
T-lymphoblast cell line CEM and its methotrexate resistant subline, colon tumor cell line
Manually annotated by BRENDA team
-
moderate enzyme expression
Manually annotated by BRENDA team
-
low enzyme expression
Manually annotated by BRENDA team
-
moderate enzyme expression
Manually annotated by BRENDA team
-
L210 mouse leukemia cells
Manually annotated by BRENDA team
-
high content
Manually annotated by BRENDA team
-
highest activity compared to other tissues
Manually annotated by BRENDA team
-
low activity in fetus, maximum at age 3 weeks, and again decline to moderate adult level
Manually annotated by BRENDA team
-
highest enzyme expression
Manually annotated by BRENDA team
-
low activity
Manually annotated by BRENDA team
-
low enzyme expression
Manually annotated by BRENDA team
-
low activity
Manually annotated by BRENDA team
-
moderate enzyme expression
Manually annotated by BRENDA team
-
low content
Manually annotated by BRENDA team
-
a neuroblastoma cell line
Manually annotated by BRENDA team
-
low enzyme expression
Manually annotated by BRENDA team
-
low enzyme expression
Manually annotated by BRENDA team
-
moderate enzyme expression
Manually annotated by BRENDA team
additional information
-
tissue specific expression
Manually annotated by BRENDA team
PDB
SCOP
CATH
ORGANISM
Aquifex aeolicus (strain VF5)
Mycoplasma pneumoniae (strain ATCC 29342 / M129)
Mycoplasma pneumoniae (strain ATCC 29342 / M129)
Mycoplasma pneumoniae (strain ATCC 29342 / M129)
MOLECULAR WEIGHT
MOLECULAR WEIGHT MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
22000
-
-
monomeric recombinant enzyme, gel filtration
23000
-
-
gel filtration
25000
-
-
gel filtration
25000
-
-
gel filtration
25000
-
-
-
25000
-
-
gel filtration, mitochondrial enzyme
25210
-
-
calculated from amino acid sequence
25220
-
-
MALDI-TOF
26500
29000
-
gel filtration, HPLC gel filtration, equilibrium ultracentrifugation
27000
-
-
gel filtration
27000
-
-
PAGE
27000
-
Q8L539
recombinant truncated enzyme, gel filtration
44000
-
-
dimeric recombinant enzyme, gel filtration
SUBUNITS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
?
-
x * 23229, calculation from nucleotide sequence
?
-
x * 23000
?
-, Q9D110
x * 23200, recombinant enzyme, SDS-PAGE
dimer
-
2 * 22000, recombinant enzyme, SDS-PAGE, the recombinant enyme exists as a mixture of monomers and dimers
dimer
-, Q81LX0
x-ray crystallography
monomer
-
1 * 27000, SDS-PAGE
monomer
-
1 * 25000, SDS-PAGE
monomer
-
1 * 23000, SDS-PAGE
monomer
Q8L539
1 * 26500, recombinant truncated enzyme, amino acid sequence determination
monomer
-
1 * 22000, recombinant enzyme, SDS-PAGE, the recombinant enyme exists as a mixture of monomers and dimers
additional information
P49914
structure modelling, overview
Crystallization/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
cocrystallization with folinate, ATP and Mg2+, sitting drop vapour diffusion method using 25% polyethylene glycol 3350, 100 mM bis-Tris pH 5.5
-, Q81LX0
purified recombinant wild-type MTHFS in a binary complex with ADP, with the N5-iminium phosphate reaction intermediate, or as an enzyme-product complex, hanging drop method at 16C, 600 nl protein solution, with or without 5 mM 5-formyltetrahydrofolate and 5 mM ATP, are equilibrated against 0.05 ml of reservoir solution containing 100 mM HEPES, pH 6.6, 20 mM MgCl2, 20 mM NiCl2, and 20% w/v PEG 3350, 2 days, X-ray diffraction structure determination and analysis
P49914
purified recombinant enzyme complexed with ADP, phosphate, and 5-formyltetrahydrofolate, hanging drop vapour diffusion method, 20C, 30 mg/ml protein with 20% PEG 4000, 5 mM ATP, and 10 mM 5-formylTHF, flash freezing of all crystals in 20% PEG 4000 and 30% ethylene glycol, X-ray diffraction structure determination and analysis at 2.5 A resolution, crystallization of the enzyme with ATP analogues ATP-gamma-S, AMP-PNP, or AMP-PCP is not successful
-
purified recombinant His-tagged wild-type and selenomethionine-labeled enzyme, hanging drop vapour diffusion method, 30 mg/ml protein in 20 mM Tris-HCl, pH 8.0, 0.1 M NaCl, 1 mM EDTA, 1 mM DTT, at room temperature, 30 mg/ml selenomethionine-labeled enzyme in 0.2 M ammonium sulfate, 0.1 M sodium acetate, 21.25% PEG 4000, 15% PEG 400, pH 4.6, at 20C, flash freezing of all crystals in a solution containing 0.17 M ammonium sulfate, 0.085 M sodium acetate, 21.25% PEG 4000, 15% PEG 400, pH 4.6, X-ray diffraction structure determination and analysis at 2.2 A resolution
-
pH STABILITY
pH STABILITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
6.5
7.5
-
below pH 6.5 and above pH 7.5, 4C, in presence of 2-mercaptoethanol, 24 h, 90% loss of activity
7
-
-
4C, 2-mercaptoethanol, 24 h, 10% loss of activity
TEMPERATURE STABILITY
TEMPERATURE STABILITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
4
-
-
extremely labile at
45
-
-
5-10 min, stable
50
-
-
5 min, 23% loss of activity, 10 min, 50% loss of activity
55
-
-
5 min, 82% loss of activity, 10 min, 91% loss of activity
GENERAL STABILITY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
non-ionic detergent, 0.1% v/v Tween 20, and 10% v/v glycerol stabilize the enzyme which is extremely labile at 4 C
-
enzyme loses activity when subjected to dialysis or concentration by ultrafiltration
-
the enzyme is stabilized by Tween 20
-, Q9D110
stabilized by non-ionic detergent Tween 20
-
OXIDATION STABILITY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
rapid loss of activity unless kept in the presence of reducing agents, e.g. DTT
-
1320
STORAGE STABILITY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
-80C, pH 7.0, 0.1% v/v Tween 20, 10% v/v glycerol, stable for several months
-
-70C, 0.1% Tween 20, stable for a long time
-
Purification/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
to near homogeneity, recombinant enzyme from Escherichia coli
Q8L539
Ni-NTA affinity chromatography and gel filtration
-, Q81LX0
recombinant His-tagged enzyme from Escherichia coli strain BL21 by nickel affinity chromatography
P49914
recombinant truncation mutant comprising residues 6-202 from Escherichia coli strain BL21(DE3) by affinity chromatography and substrate competition elution
-
recombinant His-tagged enzyme 171fold to near homogeneity from Escherichia coli strain BL21(DE3) by nickel affinity chromatography, the His-tag is removed by thrombin cleavage and dialysis
-, Q9D110
recombinant His-tagged enzyme from Escherichia coli strain BL21(DE3) by metal affinity chromatography to homogeneity
-
recombinant His-tagged enzyme from Escherichia coli strain BL21(DE3) by metal affinity chromatography to over 95% homogeneity
-
Talon metal affinity resin chromatography and Sephadex G-25 gel filtration
-, P75430
recombinant His-tagged enzyme from Escherichia coli
-
Cloned/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
DNA sequence determination and analysis, expression in Escherichia coli BL21 as full length or truncated protein, the latter lacking the mitochondrial targeting sequence, functional complementation of enzyme deficient yeast fau1 mutant, yeast strain WHY1.3.1
Q8L539
insertional mutant DNA sequence determination and analysis
-
expressed in Escherichia coli (strain Rosetta pLysS)
-, Q81LX0
cloning from brain cDNA library, expression of the His-tagged enzyme in Escherichia coli strain BL21
P49914
cytsolic enzyme
-
expression in MCF-7 mammary adenocarcinoma cell line and in SH-SY5Y neuroblastoma cell line
-
expression of truncation mutant comprising residues 6-202 in Escherichia coli strain BL21(DE3)
-
DNA and amino acid sequence determination and analysis, expression in Escherichia coli strain BL21(DE3) as N-terminally His-tagged enzyme, yield of purified recombinant enzyme depends on the growth conditions, M9 media is referred, overview
-, Q9D110
expressed in Escherichia coli BL21 Star cells and MCF-7 cells
-
expression in Escherichia coli
A0R3H2, -
DNA sequence determination and analysis, expression of His-tagged enzyme in Escherichia coli strain BL21(DE3)
-
overexpression of His-tagged enzyme in Escherichia coli strain BL21(DE3)
-
wild type and mutant enzymes are expressed in Escherichia coli strain BL21(DE3)/pSJS1244
-, P75430
expressed in Escherichia coli BL21 Star cells and MCF-7 cells
-
gene FAU1, orf YER183c, functional expression as His-tagged enzyme in Escherichia coliBL21(DE3)
-
DNA sequence determination and analysis, expression in Escherichia coli BL21(DE3) as full length or truncated protein, the latter lacking the mitochondrial targeting sequence
Q8LKF6, -
EXPRESSION
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
5,10-methenyltetrahydrofolate synthetase expression is upregulated in tumors
-
ENGINEERING
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
D154A
P49914
site-directed mutagenesis, the mutant shows 0.9% of the wild-type catalytic activity
E61A
P49914
site-directed mutagenesis, the mutant shows 8.6% of the wild-type catalytic activity
F55A
P49914
site-directed mutagenesis, the mutant shows 53.6% of the wild-type catalytic activity
F85A
P49914
site-directed mutagenesis, the mutant shows 72.3% of the wild-type catalytic activity
K10A
P49914
site-directed mutagenesis, the mutant shows 7.5% of the wild-type catalytic activity
K150A
P49914
site-directed mutagenesis, the mutant shows wild-type catalytic activity
M58A
P49914
site-directed mutagenesis, the mutant shows 121.6% of the wild-type catalytic activity
R145A
P49914
site-directed mutagenesis, the mutant shows 2.3% of the wild-type catalytic activity
R148A
P49914
site-directed mutagenesis, the mutant shows 30.7% of the wild-type catalytic activity
R14A
P49914
site-directed mutagenesis, the mutant shows 12.9% of the wild-type catalytic activity
W109A
P49914
site-directed mutagenesis, the mutant shows 39.7% of the wild-type catalytic activity
Y152A
P49914
site-directed mutagenesis, the mutant shows 24.9% of the wild-type catalytic activity
Y153A
P49914
site-directed mutagenesis, the mutant shows 3.2% of the wild-type catalytic activity
Y83A
P49914
site-directed mutagenesis, the mutant shows wild-type catalytic activity
Y151
-
able to use 5-formyltetrahydrohomofolate as a substrate
Y152A
-
increased turnover rate compared to the wild type enzyme
Y152F
-
decreased turnover rate compared to the wild type enzyme
K120A
-, P75430
the mutant shows increased Km and turnover number values for ATP and 5-formyltetrahydrofolate compared to the wild type enzyme
additional information
-
insertional mutation of the gene encoding the enzyme, At5g13050 or 28D07, reduces the growth rate of the mutant plants by 20% and delayes flowering by 1 week, and leads to accumulation of 5-formyltetrahydrofolate and glycine in leaves under photorespiratory conditions, effect of 5-formyltetrahydrofolate feeding, overview
M90A
P49914
site-directed mutagenesis, the mutant shows 49.2% of the wild-type catalytic activity
additional information
-
truncation mutant comprising residues 6-202 of the enzyme is fully active and soluble
R115A
-, P75430
the mutant shows no activity
additional information
-
disruption mutants do not evoke an altered phenotype
APPLICATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
analysis
E0IWA2
development of a functional complementation assay for 5-CHO-THF metabolism in Escherichia coli, based on deleting the gene encoding 5-FCL. The deletion mutant accumulates 5-formyltetrahydrofolate and,with glycine as sole nitrogen source, shows a growth defect, both phenotypes are complemented by bacterial or archaeal genes encoding glutamate formiminotransferase. Glutamate formiminotransferases functionally replace 5-formyltetrahydrofolate cyclo-ligases in certain prokaryotes
medicine
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the enzyme is important in cancer treatment to rescue cells from high dose levels of the anti-folate methotrexate, and to potentiate the antitumor activity of 5-fluorouracil
pharmacology
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the enzyme could be a potentially important enzyme as a target in chemotherapy