Information on EC 6.3.4.3 - formate-tetrahydrofolate ligase

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

EC NUMBER
COMMENTARY
6.3.4.3
-
RECOMMENDED NAME
GeneOntology No.
formate-tetrahydrofolate ligase
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
ATP + formate + tetrahydrofolate = ADP + phosphate + 10-formyltetrahydrofolate
show the reaction diagram
-
-
-
-
ATP + formate + tetrahydrofolate = ADP + phosphate + 10-formyltetrahydrofolate
show the reaction diagram
substrate binds to the enzyme in a random fashion, products are not released until all substrates are bound
-
ATP + formate + tetrahydrofolate = ADP + phosphate + 10-formyltetrahydrofolate
show the reaction diagram
stepwise mechanism involving a dissociable intermediate, consistent only with a sequential mechanism
-
ATP + formate + tetrahydrofolate = ADP + phosphate + 10-formyltetrahydrofolate
show the reaction diagram
stepwise reaction mechanism, formyl phosphate is a potential intermediate
-
ATP + formate + tetrahydrofolate = ADP + phosphate + 10-formyltetrahydrofolate
show the reaction diagram
direct formylation at the N-10 position, solvent oxygen is not incorporated into N10-formyltetrahydrofolate
-
ATP + formate + tetrahydrofolate = ADP + phosphate + 10-formyltetrahydrofolate
show the reaction diagram
sequential mechanism, formyl phosphate is an intermediate
-
ATP + formate + tetrahydrofolate = ADP + phosphate + 10-formyltetrahydrofolate
show the reaction diagram
the enzyme is not trifunctional showing only 10-formyl-THS synthetase activity, enzyme evolutionary considerations
-
REACTION TYPE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
formylation
-
-
-
-
formylation
-
-
formylation
-
-
formylation
P05440, P07245
;
PATHWAY
KEGG Link
MetaCyc Link
Carbon fixation pathways in prokaryotes
-
folate polyglutamylation
-
folate transformations I
-
folate transformations II
-
formate reduction to 5,10-methylenetetrahydrofolate
-
Metabolic pathways
-
Microbial metabolism in diverse environments
-
One carbon pool by folate
-
reductive acetyl coenzyme A pathway
-
SYSTEMATIC NAME
IUBMB Comments
formate:tetrahydrofolate ligase (ADP-forming)
In eukaryotes occurs as a trifunctional enzyme also having methylenetetrahydrofolate dehydrogenase (NADP+) (EC 1.5.1.5) and methenyltetrahydrofolate cyclohydrolase (EC 3.5.4.9) activity.
SYNONYMS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
10-formyl-THF synthetase
-
-
10-Formyltetrahydrofolate synthetase
-
-
-
-
10-Formyltetrahydrofolate synthetase
-
-
10-Formyltetrahydrofolate synthetase
P11586
-
10-Formyltetrahydrofolate synthetase
Q8R013
-
10-formylTHF synthetase
Q8R013
-
C(1)-tetrahydrofolate synthase
-
a monofunctional 10-formyl-tetrahydrofolate synthetase lacking the 5,10-methylene-tetrahydrofolate dehydrogenase and 5,10-methenyl-tetrahydrofolate cyclohydrolase activities typically found in the trifunctional cytoplasmic proteins
C1 synthase
P11586
-
C1-tetrahydrofolate synthase
-
-
C1-tetrahydrofolate synthase
Q6UB35
-
C1-tetrahydrofolate synthase
-
-
C1-tetrahydrofolate synthetase
Q6UB35
-
C1-THF synthase
-
-
C1-THFS
Q6UB35
-
DCS
Q8R013
-
dehydrogenasse-cyclohydrolase-synthetase
P05440, P07245
-
FHS
-
-
-
-
formate-tetrahydrofolate ligase
-
-
-
-
formate-tetrahydrofolate ligase
-
-
formate:tetrahydrofolate ligase (ADP-forming)
-
-
-
-
Formyl-THF synthetase
-
-
-
-
Formyltetrahydrofolate synthetase
-
-
-
-
Formyltetrahydrofolate synthetase
-
-
Formyltetrahydrofolate synthetase
Q15K82
-
Formyltetrahydrofolate synthetase
Q8GMP9
-
Formyltetrahydrofolate synthetase
-
-
Formyltetrahydrofolate synthetase
Q9AHS2
-
Formyltetrahydrofolate synthetase
Q9AHR6
-
Formyltetrahydrofolate synthetase
-
-
Formyltetrahydrofolate synthetase
Q8R7L3
-
Formyltetrahydrofolate synthetase
Q9AHR8
-
Formyltetrahydrofolate synthetase
P13419
-
Formyltetrahydrofolate synthetase
Q9AHS1
-
Formyltetrahydrofolate synthetase
-
-
Formyltetrahydrofolate synthetase
-
-
Formyltetrahydrofolate synthetase
-
-
Formyltetrahydrofolate synthetase
-
-
Formyltetrahydrofolate synthetase
Q8GJ02, Q9AHR7
-
Formyltetrahydrofolate synthetase
-
-
Formyltetrahydrofolate synthetase
-
-
Formyltetrahydrofolate synthetase
P11586
-
Formyltetrahydrofolate synthetase
Mesorhizobium loti, Mesorhizobium sp.
-
-
Formyltetrahydrofolate synthetase
Mesorhizobium sp. BNC1
-
-
-
Formyltetrahydrofolate synthetase
P21164
-
Formyltetrahydrofolate synthetase
Q8R013
-
Formyltetrahydrofolate synthetase
-
-
Formyltetrahydrofolate synthetase
-
-
Formyltetrahydrofolate synthetase
P05440, P07245
-
Formyltetrahydrofolate synthetase
-
-
Formyltetrahydrofolate synthetase
Q9AHR5
-
Formyltetrahydrofolate synthetase
Q9AHR4
-
Formyltetrahydrofolate synthetase
Q9AHR9
-
Formyltetrahydrofolate synthetase
Q9HI67
-
Formyltetrahydrofolate synthetase
-
-
Formyltetrahydrofolate synthetase
Q8GIN9
-
FTHFS
-
-
-
-
FTHFS
Q9AHS2
-
FTHFS
Q9AHR6
-
FTHFS
Q9AHR8
-
FTHFS
P13419
-
FTHFS
Q8GJ02, Q9AHR7
-
FTHFS
Mesorhizobium loti, Mesorhizobium sp.
-
-
FTHFS
Mesorhizobium sp. BNC1
-
-
-
FTHFS
Q9AHR5
-
FTHFS
Q9AHR4
-
FTHFS
Q8GIN9
-
methylenetetrahydrofolate dehydrogenase-methenyltetrahydrofolate cyclohydrolase-formyltetrahydrofolate synthetase
P11586
-
methylenetetrahydrofolate dehydrogenase-methenyltetrahydrofolate cyclohydrolase-formyltetrahydrofolate synthetase enzyme
Q8R013
-
MTHFD
-
-
MTHFD1
P11586
-
MTHFD1
P11586
trifunctional enzyme consisting of methylenetetrahydrofolate-dehydrogenase, methenyltetrahydrofolate-cyclohydrolase, and formyltetrahydrofolate synthetase
MTHFD1L
-
-
MTHFD1L
Q3V3R1
-
Synthetase, formyl tetrahydrofolate
-
-
-
-
Tetrahydrofolate formylase
-
-
-
-
Tetrahydrofolic formylase
-
-
-
-
THF synthase
-
MTHFDIL gene product
THFS
-
-
-
-
CAS REGISTRY NUMBER
COMMENTARY
9023-66-9
-
ORGANISM
COMMENTARY
LITERATURE
SEQUENCE CODE
SEQUENCE DB
SOURCE
isolated from environmental samples collected from different sites in Wux, China, gene fths
UniProt
Manually annotated by BRENDA team
isolated from environmental samples collected from different sites in Wux, China, gene fths
UniProt
Manually annotated by BRENDA team
fragment; isolated from environmental samples collected from different sites in Wux, China, gene fths
UniProt
Manually annotated by BRENDA team
Bacillus subtilis W168
W168
-
-
Manually annotated by BRENDA team
isolated from environmental samples collected from different sites in Wux, China, gene fths
UniProt
Manually annotated by BRENDA team
isolated from environmental samples collected from different sites in Wux, China, gene fths
UniProt
Manually annotated by BRENDA team
isolated from environmental samples collected from different sites in Wux, China, gene fths
UniProt
Manually annotated by BRENDA team
Clostridium acidi-urici
-
-
-
Manually annotated by BRENDA team
Clostridium acidi-urici
9a
-
-
Manually annotated by BRENDA team
Clostridium acidi-urici
monofunctional enzyme
-
-
Manually annotated by BRENDA team
Clostridium acidi-urici 9a
9a
-
-
Manually annotated by BRENDA team
isolated from environmental samples collected from different sites in Wux, China, gene fths
UniProt
Manually annotated by BRENDA team
wild-type and site-directed mutant enzymes H125S, H131S, and H268S
-
-
Manually annotated by BRENDA team
fragment; isolated from environmental samples collected from different sites in Wux, China, gene fths
UniProt
Manually annotated by BRENDA team
isolated from environmental samples collected from different sites in Wux, China, gene fths
-
-
Manually annotated by BRENDA team
isolated from environmental samples collected from different sites in Wux, China, gene fths
-
-
Manually annotated by BRENDA team
Enterococcus faecalis 19433
19433
-
-
Manually annotated by BRENDA team
isolated from environmental samples collected from different sites in Wux, China, gene fths
UniProt
Manually annotated by BRENDA team
strain VPI 12708
-
-
Manually annotated by BRENDA team
Eubacterium sp. VPI 12708
strain VPI 12708
-
-
Manually annotated by BRENDA team
-
SwissProt
Manually annotated by BRENDA team
mutation in MTHFD can act as a risk factor in human neural tube defects, however, it is unlikely that this gene plays a major role in the etiology of neural tube defects
-
-
Manually annotated by BRENDA team
trifunctional enzyme
SwissProt
Manually annotated by BRENDA team
trifunctional enzyme with 10-formyltetrahydrofolate synthetase, EC 6.3.4.3, 5,10-methenyltetrahydrofolate cyclohydrolase, EC 3.5.4.9, and 5,10-methylenetetrahydrofolate dehydrogenase activity, EC 1.5.1.5
-
-
Manually annotated by BRENDA team
isolated from environmental samples collected from different sites in Wux, China, gene fths
-
-
Manually annotated by BRENDA team
Mesorhizobium sp.
isolated from environmental samples collected from different sites in Wux, China, gene fths
-
-
Manually annotated by BRENDA team
Mesorhizobium sp. BNC1
isolated from environmental samples collected from different sites in Wux, China, gene fths
-
-
Manually annotated by BRENDA team
Micrococcus luteus 4698
4698
-
-
Manually annotated by BRENDA team
isolated from environmental samples collected from different sites in Wux, China, gene fths
UniProt
Manually annotated by BRENDA team
previously referred to as Clostridium thermoaceticum
UniProt
Manually annotated by BRENDA team
25238, weak activity
-
-
Manually annotated by BRENDA team
DCS, complete gene and exon 27; gene mthfd1 encodes the cytosolic isozyme which is a trifunctional methylenetetrahydrofolate dehydrogenase-methenyltetrahydrofolate cyclohydrolase-formyltetrahydrofolate synthetase enzyme DCS, a mitochondrial monofunctional 10-formyltetrahydrofolate synthetase isozyme is encoded by a different gene
Q8R013
SwissProt
Manually annotated by BRENDA team
trifunctional enzyme with 10-formyltetrahydrofolate synthetase, EC 6.3.4.3, 5,10-methenyltetrahydrofolate cyclohydrolase, EC 3.5.4.9, and 5,10-methylenetetrahydrofolate dehydrogenase activity, EC 1.5.1.5
-
-
Manually annotated by BRENDA team
trifunctional enzyme with 10-formyltetrahydrofolate synthetase, EC 6.3.4.3, 5,10-methenyltetrahydrofolate cyclohydrolase, EC 3.5.4.9, and 5,10-methylenetetrahydrofolate dehydrogenase activity, EC 1.5.1.5
-
-
Manually annotated by BRENDA team
Peptostreptococcus anaerobius 27337
27337
-
-
Manually annotated by BRENDA team
Pigeon
-
-
-
Manually annotated by BRENDA team
monofunctional enzyme
-
-
Manually annotated by BRENDA team
Proteus mirabilis 25433
25433
-
-
Manually annotated by BRENDA team
isolated from environmental samples collected from different sites in Wux, China, gene fths
-
-
Manually annotated by BRENDA team
isolated from environmental samples collected from different sites in Wux, China, gene fths
-
-
Manually annotated by BRENDA team
trifunctional enzyme with 10-formyltetrahydrofolate synthetase, EC 6.3.4.3, 5,10-methenyltetrahydrofolate cyclohydrolase, EC 3.5.4.9, and 5,10-methylenetetrahydrofolate dehydrogenase activity, EC 1.5.1.5
-
-
Manually annotated by BRENDA team
isolated from environmental samples collected from different sites in Wux, China, gene fths
-
-
Manually annotated by BRENDA team
isolated from environmental samples collected from different sites in Wux, China, gene fths
-
-
Manually annotated by BRENDA team
isolated from environmental samples collected from different sites in Wux, China, gene fths
-
-
Manually annotated by BRENDA team
isolated from environmental samples collected from different sites in Wux, China, gene fths
UniProt
Manually annotated by BRENDA team
fragment; isolated from environmental samples collected from different sites in Wux, China, gene fths
Q9AHR4
UniProt
Manually annotated by BRENDA team
Staphylococcus epidermidis 14990
14990
-
-
Manually annotated by BRENDA team
trifunctional enzyme with 10-formyltetrahydrofolate synthetase, EC 6.3.4.3, 5,10-methenyltetrahydrofolate cyclohydrolase, EC 3.5.4.9, and 5,10-methylenetetrahydrofolate dehydrogenase activity, EC 1.5.1.5
-
-
Manually annotated by BRENDA team
isolated from environmental samples collected from different sites in Wux, China, gene fths
UniProt
Manually annotated by BRENDA team
isolated from environmental samples collected from different sites in Wux, China, gene fths
UniProt
Manually annotated by BRENDA team
isolated from environmental samples collected from different sites in Wux, China, gene fths
-
-
Manually annotated by BRENDA team
isolated from environmental samples collected from different sites in Wux, China, gene fths
UniProt
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
metabolism
-
FTHFS is a key enzyme of the Wood-Ljungdahl pathway
metabolism
Q9AHS2
FTHFS is a key enzyme of the Wood-Ljungdahl pathway
SUBSTRATE
PRODUCT                      
REACTION DIAGRAM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
(R,S)-tetrahydrofolate + ATP + formate
?
show the reaction diagram
-
-
-
-
r
ADP + carbamoylphosphate + tetrahydrofolate
ATP + ?
show the reaction diagram
-
-
-
?
ADP + phosphate + 10-formyltetrahydrofolate
?
show the reaction diagram
Clostridium cylindrosporum, Clostridium acidi-urici
-
ATP production. The relative concentration of formylated and unformylated folate coenzymes may be a significant regulatory parameter in the purine-fermenting Clostridia
-
-
-
ATP + (6R,S)-tetrahydrofolate pteroylpentaglutamate
ADP + phosphate + 10-formyltetrahydrofolate pteroylpentaglutamate
show the reaction diagram
-
-
-
-
?
ATP + (6R,S)-tetrahydrofolate pteroyltriglutamate
ADP + phosphate + 10-formyltetrahydrofolate pteroyltriglutamate
show the reaction diagram
-
-
-
-
?
ATP + formate
ADP + HCOOPO32-
show the reaction diagram
-
formate kinase reaction, sequential random bi bi mechanism
-
-
ATP + formate + (6R,S)-tetrahydrofolate monoglutamate
ADP + phosphate + 10-formyltetrahydrofolate monoglutamate
show the reaction diagram
-
-
-
-
?
ATP + formate + tetrahydrofolate
ADP + phosphate + 10-formyltetrahydrofolate
show the reaction diagram
-
-
-
-
ATP + formate + tetrahydrofolate
ADP + phosphate + 10-formyltetrahydrofolate
show the reaction diagram
-
-
-
-
ATP + formate + tetrahydrofolate
ADP + phosphate + 10-formyltetrahydrofolate
show the reaction diagram
-
-
-
-
ATP + formate + tetrahydrofolate
ADP + phosphate + 10-formyltetrahydrofolate
show the reaction diagram
-
-
-
-
ATP + formate + tetrahydrofolate
ADP + phosphate + 10-formyltetrahydrofolate
show the reaction diagram
-
-
-
-
ATP + formate + tetrahydrofolate
ADP + phosphate + 10-formyltetrahydrofolate
show the reaction diagram
-
-
-
-
ATP + formate + tetrahydrofolate
ADP + phosphate + 10-formyltetrahydrofolate
show the reaction diagram
-
-
-
-
ATP + formate + tetrahydrofolate
ADP + phosphate + 10-formyltetrahydrofolate
show the reaction diagram
-
-
-
-
ATP + formate + tetrahydrofolate
ADP + phosphate + 10-formyltetrahydrofolate
show the reaction diagram
-
-
-
?
ATP + formate + tetrahydrofolate
ADP + phosphate + 10-formyltetrahydrofolate
show the reaction diagram
-
-
-
-
?
ATP + formate + tetrahydrofolate
ADP + phosphate + 10-formyltetrahydrofolate
show the reaction diagram
-
-
-
-
ATP + formate + tetrahydrofolate
ADP + phosphate + 10-formyltetrahydrofolate
show the reaction diagram
-
-
-
?
ATP + formate + tetrahydrofolate
ADP + phosphate + 10-formyltetrahydrofolate
show the reaction diagram
-
-
-
?
ATP + formate + tetrahydrofolate
ADP + phosphate + 10-formyltetrahydrofolate
show the reaction diagram
-
-
-
-
?
ATP + formate + tetrahydrofolate
ADP + phosphate + 10-formyltetrahydrofolate
show the reaction diagram
-
-
-
-
ATP + formate + tetrahydrofolate
ADP + phosphate + 10-formyltetrahydrofolate
show the reaction diagram
-
-
-
-
ATP + formate + tetrahydrofolate
ADP + phosphate + 10-formyltetrahydrofolate
show the reaction diagram
-
-
-
-
ATP + formate + tetrahydrofolate
ADP + phosphate + 10-formyltetrahydrofolate
show the reaction diagram
-
-
-
-
ATP + formate + tetrahydrofolate
ADP + phosphate + 10-formyltetrahydrofolate
show the reaction diagram
-
-
-
-
ATP + formate + tetrahydrofolate
ADP + phosphate + 10-formyltetrahydrofolate
show the reaction diagram
-
-
-
-
ATP + formate + tetrahydrofolate
ADP + phosphate + 10-formyltetrahydrofolate
show the reaction diagram
-
-
-
-
ATP + formate + tetrahydrofolate
ADP + phosphate + 10-formyltetrahydrofolate
show the reaction diagram
-
-
-
-
ATP + formate + tetrahydrofolate
ADP + phosphate + 10-formyltetrahydrofolate
show the reaction diagram
-
-
-
-
ATP + formate + tetrahydrofolate
ADP + phosphate + 10-formyltetrahydrofolate
show the reaction diagram
-
-
-
-
ATP + formate + tetrahydrofolate
ADP + phosphate + 10-formyltetrahydrofolate
show the reaction diagram
-
-
-
-
ATP + formate + tetrahydrofolate
ADP + phosphate + 10-formyltetrahydrofolate
show the reaction diagram
-
-
-
-
ATP + formate + tetrahydrofolate
ADP + phosphate + 10-formyltetrahydrofolate
show the reaction diagram
-
-
-
-
ATP + formate + tetrahydrofolate
ADP + phosphate + 10-formyltetrahydrofolate
show the reaction diagram
-
-
-
-
ATP + formate + tetrahydrofolate
ADP + phosphate + 10-formyltetrahydrofolate
show the reaction diagram
-
-
-
-
ATP + formate + tetrahydrofolate
ADP + phosphate + 10-formyltetrahydrofolate
show the reaction diagram
-
-
-
-
ATP + formate + tetrahydrofolate
ADP + phosphate + 10-formyltetrahydrofolate
show the reaction diagram
-
-
-
-
ATP + formate + tetrahydrofolate
ADP + phosphate + 10-formyltetrahydrofolate
show the reaction diagram
-
-
-
-
ATP + formate + tetrahydrofolate
ADP + phosphate + 10-formyltetrahydrofolate
show the reaction diagram
-
-
-
-
ATP + formate + tetrahydrofolate
ADP + phosphate + 10-formyltetrahydrofolate
show the reaction diagram
-
-
-
-
ATP + formate + tetrahydrofolate
ADP + phosphate + 10-formyltetrahydrofolate
show the reaction diagram
-
-
-
-
ATP + formate + tetrahydrofolate
ADP + phosphate + 10-formyltetrahydrofolate
show the reaction diagram
-
-
-
-
ATP + formate + tetrahydrofolate
ADP + phosphate + 10-formyltetrahydrofolate
show the reaction diagram
-
-
-
-
ATP + formate + tetrahydrofolate
ADP + phosphate + 10-formyltetrahydrofolate
show the reaction diagram
-
-
-
-
ATP + formate + tetrahydrofolate
ADP + phosphate + 10-formyltetrahydrofolate
show the reaction diagram
-
-
-
-
ATP + formate + tetrahydrofolate
ADP + phosphate + 10-formyltetrahydrofolate
show the reaction diagram
-
-
-
-
ATP + formate + tetrahydrofolate
ADP + phosphate + 10-formyltetrahydrofolate
show the reaction diagram
-
-
-
-
ATP + formate + tetrahydrofolate
ADP + phosphate + 10-formyltetrahydrofolate
show the reaction diagram
-
-
-
-
ATP + formate + tetrahydrofolate
ADP + phosphate + 10-formyltetrahydrofolate
show the reaction diagram
Clostridium acidi-urici
-
-
-
-
ATP + formate + tetrahydrofolate
ADP + phosphate + 10-formyltetrahydrofolate
show the reaction diagram
Clostridium acidi-urici
-
-
-
-
ATP + formate + tetrahydrofolate
ADP + phosphate + 10-formyltetrahydrofolate
show the reaction diagram
Clostridium acidi-urici
-
-
-
-
ATP + formate + tetrahydrofolate
ADP + phosphate + 10-formyltetrahydrofolate
show the reaction diagram
Clostridium acidi-urici
-
-
-
-
ATP + formate + tetrahydrofolate
ADP + phosphate + 10-formyltetrahydrofolate
show the reaction diagram
Clostridium acidi-urici
-
-
-
-
ATP + formate + tetrahydrofolate
ADP + phosphate + 10-formyltetrahydrofolate
show the reaction diagram
Clostridium acidi-urici
-
-
-
-
ATP + formate + tetrahydrofolate
ADP + phosphate + 10-formyltetrahydrofolate
show the reaction diagram
Clostridium acidi-urici
-
-
-
-
ATP + formate + tetrahydrofolate
ADP + phosphate + 10-formyltetrahydrofolate
show the reaction diagram
-
-
-
-
ATP + formate + tetrahydrofolate
ADP + phosphate + 10-formyltetrahydrofolate
show the reaction diagram
-
-
-
-
ATP + formate + tetrahydrofolate
ADP + phosphate + 10-formyltetrahydrofolate
show the reaction diagram
-
-
-
-
ATP + formate + tetrahydrofolate
ADP + phosphate + 10-formyltetrahydrofolate
show the reaction diagram
-
-
-
-
ATP + formate + tetrahydrofolate
ADP + phosphate + 10-formyltetrahydrofolate
show the reaction diagram
-
-
-
?
ATP + formate + tetrahydrofolate
ADP + phosphate + 10-formyltetrahydrofolate
show the reaction diagram
P21164
-
-
?
ATP + formate + tetrahydrofolate
ADP + phosphate + 10-formyltetrahydrofolate
show the reaction diagram
P21164
-
-
?
ATP + formate + tetrahydrofolate
ADP + phosphate + 10-formyltetrahydrofolate
show the reaction diagram
-
-
-
-
ATP + formate + tetrahydrofolate
ADP + phosphate + 10-formyltetrahydrofolate
show the reaction diagram
-
-
-
-
ATP + formate + tetrahydrofolate
ADP + phosphate + 10-formyltetrahydrofolate
show the reaction diagram
-, Q83WS0
-
-
?
ATP + formate + tetrahydrofolate
ADP + phosphate + 10-formyltetrahydrofolate
show the reaction diagram
-, Q6UB35
-
-
?
ATP + formate + tetrahydrofolate
ADP + phosphate + 10-formyltetrahydrofolate
show the reaction diagram
Q8R013
-
-
-
r
ATP + formate + tetrahydrofolate
ADP + phosphate + 10-formyltetrahydrofolate
show the reaction diagram
-
-
-
-
?
ATP + formate + tetrahydrofolate
ADP + phosphate + 10-formyltetrahydrofolate
show the reaction diagram
P11586
-
-
-
?
ATP + formate + tetrahydrofolate
ADP + phosphate + 10-formyltetrahydrofolate
show the reaction diagram
-
r
-
-
ATP + formate + tetrahydrofolate
ADP + phosphate + 10-formyltetrahydrofolate
show the reaction diagram
-
r
-
-
ATP + formate + tetrahydrofolate
ADP + phosphate + 10-formyltetrahydrofolate
show the reaction diagram
-
r
-
-
ATP + formate + tetrahydrofolate
ADP + phosphate + 10-formyltetrahydrofolate
show the reaction diagram
-
r
-
-
ATP + formate + tetrahydrofolate
ADP + phosphate + 10-formyltetrahydrofolate
show the reaction diagram
-
r
-
-
ATP + formate + tetrahydrofolate
ADP + phosphate + 10-formyltetrahydrofolate
show the reaction diagram
-, Q6UB35
trifuntional enzyme having 10-formyl-tetrahydrofolate synthetase, 5,10-methylene-tetrahydrofolate cyclohydrolase and 5,10-methylene-tetrahydrofolate dehydrogenase activity
-
?
ATP + formate + tetrahydrofolate
ADP + phosphate + 10-formyltetrahydrofolate
show the reaction diagram
-, Q83WS0
FtfL activity is required for methylotrophic growth
-
?
ATP + formate + tetrahydrofolate
ADP + phosphate + 10-formyltetrahydrofolate
show the reaction diagram
Q8R013
flow of one-carbon units through cytoplasmic and mitochondrial folate pathways, overview
-
-
r
ATP + formate + tetrahydrofolate
ADP + phosphate + 10-formyltetrahydrofolate
show the reaction diagram
Eubacterium sp. VPI 12708, Staphylococcus epidermidis 14990, Clostridium acidi-urici 9a, Proteus mirabilis 25433, Micrococcus luteus 4698, Enterococcus faecalis 19433, Bacillus subtilis W168, Peptostreptococcus anaerobius 27337
-
-
-
-
ATP + formate + tetrahydrofolate
?
show the reaction diagram
-
enzyme of one-carbon metabolism
-
-
-
ATP + formate + tetrahydrofolate
?
show the reaction diagram
-
two different physiological roles: 1. Functions anabolically in most organisms to activate formate via the forward reaction, and brings it into the one-carbon metabolic pool as N10-formyltetrahydrofolate, 2. In purine-fermenting bacteria the enzyme probably functions catabolically in the terminal step of the purine degradative pathway. This reaction may be responsible for ATP production in these organisms
-
-
-
ATP + formate + tetrahydrofolate
?
show the reaction diagram
-
the trifunctional enzyme is involved in the interconversion of one-carbon adducts of tetrahydrofolate
-
-
-
ATP + formate + tetrahydrofolate
?
show the reaction diagram
Clostridium acidi-urici
-
the enzyme is responsible for the recruitment of single carbon units from the formate pool into a variety of folate-dependent biosynthetic pathways
-
-
-
ATP + formate + tetrahydrofolate
?
show the reaction diagram
-
rate-determining step in the conversion of formate to Ser
-
-
-
ATP + formate + tetrahydropteroyl-(Glu)n
ADP + phosphate + 10-formyltetrahydropteroyl-(Glu)n
show the reaction diagram
-
-
-
-
-
ATP + formate + tetrahydropteroyl-(Glu)n
ADP + phosphate + 10-formyltetrahydropteroyl-(Glu)n
show the reaction diagram
-
r, n: 3
-
-
ATP + formate + tetrahydropteroyl-(Glu)n
ADP + phosphate + 10-formyltetrahydropteroyl-(Glu)n
show the reaction diagram
-
n: 1-5
-
-
-
ATP + formate + tetrahydropteroyl-(Glu)n
ADP + phosphate + 10-formyltetrahydropteroyl-(Glu)n
show the reaction diagram
-
n: 1-5
-
-
-
ATP + formate + tetrahydropteroyl-(Glu)n
ADP + phosphate + 10-formyltetrahydropteroyl-(Glu)n
show the reaction diagram
-
n: 1-6
-
-
-
ATP + formate + tetrahydropteroyl-(Glu)n
ADP + phosphate + 10-formyltetrahydropteroyl-(Glu)n
show the reaction diagram
-
r, n: 2,3
-
-
Carbamoyl phosphate + ADP
? + ATP
show the reaction diagram
-
-
-
-
Carbamoyl phosphate + ADP
? + ATP
show the reaction diagram
-
-
-
-
dATP + formate + tetrahydrofolate
dADP + phosphate + 10-formyltetrahydrofolate
show the reaction diagram
-
37% of the activity relative to ATP
-
-
-
tetrahydrofolate + formate + ATP
10-formyltetrahydrofolate + ADP + phosphate
show the reaction diagram
-
monofunctional enzyme
-
-
?
tetrahydrofolate + formate + ATP
10-formyltetrahydrofolate + ADP + phosphate
show the reaction diagram
-
monofunctional enzyme similar in structure to the cytoplasmatic trifunctional enzyme, dehydrogenase and cyclohydrolase activities are silent due to mutations of critical binding and catalytic residues
mitochondria also use formyltetrahydrofolate to produce formylmethionyl-tRNA to initiate protein synthesis
-
r
tetrahydrofolate + formate + ATP
10-formyltetrahydrofolate + ADP + phosphate
show the reaction diagram
-
trifunctional enzyme exhibits synthetase, dehydrogenase and cyclohydrogenase activities
-
-
r
tetrahydrofolate + formate + ATP
10-formyltetrahydrofolate + ADP + phosphate
show the reaction diagram
P05440, P07245
trifunctional enzyme exhibits synthetase, dehydrogenase and cyclohydrolase activities
-
-
r
formate + ATP + tetrahydrofolate
10-formyltetrahydrofolate + ADP + phosphate
show the reaction diagram
-
synthetase activity of MTHFD1
-
-
-
additional information
?
-
-
enzyme is involved in the folate-mediated one-carbon metabolism, overview
-
-
-
additional information
?
-
Q6UB35
the enzyme may participate in the progression of colorectal cancer by conferring growth advantage
-
-
-
additional information
?
-
-
(MTHFD1) is a trifunctional enzyme that interconverts tetrahydrofolate derivatives for nucleotide synthesis
-
-
-
additional information
?
-
-
Leishmania possess a second cytoplasmic pathway for 10-formyltetrahydrofolate synthesis through FTL
-
-
-
additional information
?
-
P05440, P07245
the presence of cytoplasmic and mitochondrial isoforms of a trifunctional dehydrogenase-cyclohydrolase-synthetase support a model wherin the mitochondria can produce fromate which can be used by the cytoplasmic enzymes for the synthesis of purins and for methylation reactions
-
-
-
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
ADP + phosphate + 10-formyltetrahydrofolate
?
show the reaction diagram
Clostridium cylindrosporum, Clostridium acidi-urici
-
ATP production. The relative concentration of formylated and unformylated folate coenzymes may be a significant regulatory parameter in the purine-fermenting Clostridia
-
-
-
ATP + formate + tetrahydrofolate
ADP + phosphate + 10-formyltetrahydrofolate
show the reaction diagram
-
-
-
?
ATP + formate + tetrahydrofolate
ADP + phosphate + 10-formyltetrahydrofolate
show the reaction diagram
-
-
-
?
ATP + formate + tetrahydrofolate
ADP + phosphate + 10-formyltetrahydrofolate
show the reaction diagram
-
-
-
?
ATP + formate + tetrahydrofolate
ADP + phosphate + 10-formyltetrahydrofolate
show the reaction diagram
-
-
-
?
ATP + formate + tetrahydrofolate
ADP + phosphate + 10-formyltetrahydrofolate
show the reaction diagram
P21164
-
-
?
ATP + formate + tetrahydrofolate
ADP + phosphate + 10-formyltetrahydrofolate
show the reaction diagram
P21164
-
-
?
ATP + formate + tetrahydrofolate
ADP + phosphate + 10-formyltetrahydrofolate
show the reaction diagram
-, Q6UB35
-
-
?
ATP + formate + tetrahydrofolate
ADP + phosphate + 10-formyltetrahydrofolate
show the reaction diagram
-, Q83WS0
FtfL activity is required for methylotrophic growth
-
?
ATP + formate + tetrahydrofolate
ADP + phosphate + 10-formyltetrahydrofolate
show the reaction diagram
Q8R013
flow of one-carbon units through cytoplasmic and mitochondrial folate pathways, overview
-
-
r
ATP + formate + tetrahydrofolate
?
show the reaction diagram
-
enzyme of one-carbon metabolism
-
-
-
ATP + formate + tetrahydrofolate
?
show the reaction diagram
-
two different physiological roles: 1. Functions anabolically in most organisms to activate formate via the forward reaction, and brings it into the one-carbon metabolic pool as N10-formyltetrahydrofolate, 2. In purine-fermenting bacteria the enzyme probably functions catabolically in the terminal step of the purine degradative pathway. This reaction may be responsible for ATP production in these organisms
-
-
-
ATP + formate + tetrahydrofolate
?
show the reaction diagram
-
the trifunctional enzyme is involved in the interconversion of one-carbon adducts of tetrahydrofolate
-
-
-
ATP + formate + tetrahydrofolate
?
show the reaction diagram
Clostridium acidi-urici
-
the enzyme is responsible for the recruitment of single carbon units from the formate pool into a variety of folate-dependent biosynthetic pathways
-
-
-
ATP + formate + tetrahydrofolate
?
show the reaction diagram
-
rate-determining step in the conversion of formate to Ser
-
-
-
tetrahydrofolate + formate + ATP
10-formyltetrahydrofolate + ADP + phosphate
show the reaction diagram
-
monofunctional enzyme
-
-
?
tetrahydrofolate + formate + ATP
10-formyltetrahydrofolate + ADP + phosphate
show the reaction diagram
-
monofunctional enzyme similar in structure to the cytoplasmatic trifunctional enzyme, dehydrogenase and cyclohydrolase activities are silent due to mutations of critical binding and catalytic residues
mitochondria also use formyltetrahydrofolate to produce formylmethionyl-tRNA to initiate protein synthesis
-
r
tetrahydrofolate + formate + ATP
10-formyltetrahydrofolate + ADP + phosphate
show the reaction diagram
-
trifunctional enzyme exhibits synthetase, dehydrogenase and cyclohydrogenase activities
-
-
r
tetrahydrofolate + formate + ATP
10-formyltetrahydrofolate + ADP + phosphate
show the reaction diagram
P05440, P07245
trifunctional enzyme exhibits synthetase, dehydrogenase and cyclohydrolase activities
-
-
r
formate + ATP + tetrahydrofolate
10-formyltetrahydrofolate + ADP + phosphate
show the reaction diagram
-
synthetase activity of MTHFD1
-
-
-
additional information
?
-
-
enzyme is involved in the folate-mediated one-carbon metabolism, overview
-
-
-
additional information
?
-
Q6UB35
the enzyme may participate in the progression of colorectal cancer by conferring growth advantage
-
-
-
additional information
?
-
-
(MTHFD1) is a trifunctional enzyme that interconverts tetrahydrofolate derivatives for nucleotide synthesis
-
-
-
additional information
?
-
-
Leishmania possess a second cytoplasmic pathway for 10-formyltetrahydrofolate synthesis through FTL
-
-
-
additional information
?
-
P05440, P07245
the presence of cytoplasmic and mitochondrial isoforms of a trifunctional dehydrogenase-cyclohydrolase-synthetase support a model wherin the mitochondria can produce fromate which can be used by the cytoplasmic enzymes for the synthesis of purins and for methylation reactions
-
-
-
METALS and IONS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
Ca2+
-
the requirement for a divalent cation is most effectively satisfied by Mg2+. Mn2+ and Ca2+ can substitute for Mg2+
Ca2+
-
Km for CaCl2: 0.21 mM; the requirement for a divalent cation is most effectively satisfied by Mg2+. Mn2+ and Ca2+ can substitute for Mg2+
Cs+
-
specific monovalent cations required for maximal activity, order of effectiveness: NH4+, Tl+, Rb+ ~ K+, Cs+, Na+ ~ Li+
Cs+
-
activity is stimulated by various monovalent cations. The order of effectiveness of 10, 50 or 100 mM salts: Rb+, K+, NH4+, Na+, Cs+
Divalent metal ion
-
the requirement for a divalent cation is most effectively satisfied by Mg2+. Mn2+ and Ca2+ can substitute for Mg2+
Divalent metal ion
-
the requirement for a divalent cation is most effectively satisfied by Mg2+. Mn2+ and Ca2+ can substitute for Mg2+
K+
-
specific monovalent cations required for maximal activity, order of effectiveness: NH4+, Tl+, Rb+ ~ K+, Cs+, Na+ ~ Li+
K+
-
activity is stimulated by various monovalent cations. The order of effectiveness of 10, 50 or 100 mM salts: Rb+, K+, NH4+, Na+, Cs+
K+
-
stimulates formate kinase reaction, Km: 8.7 mM
K+
-
Km: 4 mM; K+ or NH4+ required
K+
P21164
monovalent cation required for activity
K+
-
activates at 100-200 mM, inhibitory above 200 mM
Li+
-
specific monovalent cations required for maximal activity, order of effectiveness: NH4+, Tl+, Rb+ ~ K+, Cs+, Na+ ~ Li+
Mg2+
-
the requirement for a divalent cation is most effectively satisfied by Mg2+. Mn2+ and Ca2+ can substitute for Mg2+
Mg2+
-
the requirement for a divalent cation is most effectively satisfied by Mg2+. Mn2+ and Ca2+ can substitute for Mg2+
Mg2+
-
Km for MgCl2: 0.44 mM; the requirement for a divalent cation is most effectively satisfied by Mg2+. Mn2+ and Ca2+ can substitute for Mg2+
Mg2+
-
stimulates formate kinase reaction, Km: 0.88 mM
Mg2+
-
stimulates
Mg2+
-
-
Mn2+
-
the requirement for a divalent cation is most effectively satisfied by Mg2+. Mn2+ and Ca2+ can substitute for Mg2+
Mn2+
-
Km for MnCl2: 0.23 mM; the requirement for a divalent cation is most effectively satisfied by Mg2+. Mn2+ and Ca2+ can substitute for Mg2+
Monovalent cations
-
specific monovalent cations required for maximal activity, order of effectiveness: NH4+, Tl+, Rb+ ~ K+, Cs+, Na+ ~ Li+
Monovalent cations
-
-
Monovalent cations
-
activity is stimulated by various monovalent cations. The order of effectiveness of 10, 50 or 100 mM salts: Rb+, K+,NH4+, Na+,Cs+
Na+
-
specific monovalent cations required for maximal activity, order of effectiveness: NH4+, Tl+, Rb+ ~ K+, Cs+, Na+ ~ Li+
Na+
-
activity is stimulated by various monovalent cations. The order of effectiveness of 10, 50 or 100 mM salts: Rb+, K+, NH4+, Na+, Cs+
NH4+
-
specific monovalent cations required for maximal activity, order of effectiveness: NH4+, Tl+, Rb+ ~ K+, Cs+, Na+ ~ Li+
NH4+
-
activates forward and reverse reaction
NH4+
-
activity is stimulated by various monovalent cations. The order of effectiveness of 10, 50 or 100 mM salts: Rb+, K+, NH4+, Na+, Cs+
NH4+
-
Km: 1.8 mM; K+ or NH4+ required
NH4+
P21164
monovalent cation required for activity
NH4+
-
activates, maximal at 100 mM
Rb+
-
specific monovalent cations required for maximal activity, order of effectiveness: NH4+, Tl+, Rb+ ~ K+, Cs+, Na+ ~ Li+
Rb+
-
activates synthesis of 10-formyltetrahydrofolate
Rb+
-
activity is stimulated by various monovalent cations. The order of effectiveness of 10, 50 or 100 mM salts: Rb+, K+, NH4+, Na+, Cs+
Tl+
-
specific monovalent cations required for maximal activity, order of effectiveness: NH4+, Tl+, Rb+ ~ K+, Cs+, Na+ ~ Li+
INHIBITORS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
(2S)-2-[[4-[(6aR)-3-amino-1,9-dioxo-5,6,6a,7-tetrahydro-4H-imidazol[3,4-f]pteridin-8-yl]benzoyl]amino]pentanedioate
-
5,10-formyltetrahydrofolate substrate analogue inhibits dehydrogenase activity
2,2'-dipyridyl disulfide
-
-
2,4-diamino-6-(3,4-dichlorophenoxy)-quinazoline
-
-
2,4-diamino-6-benzyl-5-(3-phenylpropyl)-pyrimidine
-
-
5,5'-dithiobis(2-nitrobenzoate)
-
-
acetyl phosphate
-
inhibits ATP synthesis reaction from carbamoyl phosphate and ADP, and synthesis of 10-formyltetrahydrofolate
Adenylyl imidodiphosphate
-
competitive to ATP
ADP
-
competitive to ATP
alpha,beta-methyleneadenosine 5'-triphosphate
-
competitive to ATP
beta,gamma-methyleneadenosine 5'-triphosphate
-
competitive to ATP
Ca2+
-
in presence of Mg2+
Carbamoyl phosphate
-
-
Fluorescein mercuric acetate
-
-
formate
-
inhibits ATP synthesis reaction from carbamoyl phosphate and ADP
Formyltetrahydrofolate
-
-
methotrexate
-
-
Mn2+
-
in presence of Mg2+
p-hydroxymercuribenzoate
-
-
phosphate
-
inhibits ATP synthesis reaction from carbamoyl phosphate and ADP
Phosphonoacetate
-
inhibits ATP synthesis reaction from carbamoyl phosphate and ADP, and synthesis of 10-formyltetrahydrofolate
pteroylpentaglutamate
-
-
Tetranitromethane
-
-
Zn2+
-
in presence of Mg2+
ACTIVATING COMPOUND
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
spermine
-
stimulates activity only in absence of NH4+
KM VALUE [mM]
KM VALUE [mM] Maximum
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.5
-
(6R,S)-tetrahydrofolate monoglutamate
-
above, recombinant enzyme, 30C
0.0036
-
(6R,S)-tetrahydrofolate pteroylpentaglutamate
-
recombinant enzyme, 30C
0.016
-
(6R,S)-tetrahydrofolate pteroyltriglutamate
-
recombinant enzyme, 30C
0.032
-
ADP
-
ATP synthesis from carbamoylphosphate
0.13
-
ADP
-
formyltetrahydrofolate synthesis
0.13
-
ADP
-
tetrahydrofolate, mutant enzyme K71Q
0.012
-
ATP
-
reaction with tetrahydropteroyl-Glu5
0.021
-
ATP
-, Q83WS0
30C, pH 8.0
0.0286
-
ATP
-
mutant R653Q
0.0302
-
ATP
-
wild type
0.04
-
ATP
-
recombinant enzyme, 30C, with substrate (6R,S)-tetrahydrofolate pteroyltriglutamate or (6R,S)-tetrahydrofolate pteroylpentaglutamate and formate
0.062
-
ATP
-
reaction with tetrahydropteroyl-Glu3
0.087
-
ATP
-
27C, pH 7.0, wild-type FTHFS
0.094
-
ATP
-
reaction with tetrahydrofolate
0.094
-
ATP
-
ATP, reaction with tetrahydropteroyl-Glu2; reaction with tetrahydrofolate
0.16
-
ATP
-
27C, pH 7.0, R97S mutant FTHFS
0.2
-
ATP
-
above, recombinant enzyme, 30C, with substrate (6R,S)-tetrahydrofolate monoglutamate and formate
11.9
-
Carbamoyl phosphate
-
-
0.035
-
formate
-
reaction with tetrahydropteroyl-Glu5
0.0367
-
formate
-
wild type
0.0371
-
formate
-
mutant R653Q
0.15
-
formate
-
recombinant enzyme, 30C, with substrate (6R,S)-tetrahydrofolate pteroylpentaglutamate
0.166
-
formate
-
-
0.43
-
formate
-
reaction with tetrahydropteroyl-Glu3
0.44
-
formate
-
recombinant enzyme, 30C, with substrate (6R,S)-tetrahydrofolate pteroyltriglutamate
0.46
-
formate
-
27C, pH 7.0, wild-type FTHFS
0.95
-
formate
-
27C, pH 7.0, R97S mutant FTHFS
0.98
-
formate
-
reaction with tetrahydropteroyl-Glu2
5.4
-
formate
-
-
6.7
-
formate
-
wild-type enzyme
7.6
-
formate
-
reaction with tetrahydrofolate
8.2
-
formate
-
mutant enzyme H125S
11.8
-
formate
-
recombinant enzyme, 30C, with substrate (6R,S)-tetrahydrofolate monoglutamate
12.1
-
formate
-
mutant enzyme K71Q
16
-
formate
-
-
20.2
-
formate
-
mutant enzyme H131S
22
-
formate
-, Q83WS0
30C, pH 8.0
0.056
-
MgATP2-
-
-
0.067
-
MgATP2-
-
-
0.086
-
MgATP2-
-
-
0.12
-
MgATP2-
-
N10-formyltetrahydropteroyl-Glu3
0.14
-
MgATP2-
-
formate, reaction with tetrahydropteroyl-Glu4
0.26
-
MgATP2-
-
mutant enzyme K71Q
0.4
-
MgATP2-
-
mutant enzyme H131S
10
-
N10-formyltetrahydrofolate
-
-
0.015
-
tetrahydrofolate
-
-
0.032
0.077
tetrahydrofolate
-
ATP synthesis
0.04
-
tetrahydrofolate
-
-
0.23
-
tetrahydrofolate
-
-
0.23
-
tetrahydrofolate
-
MgATP2-, wild-type enzyme
0.27
-
tetrahydrofolate
-
formyltretrahydrofolate synthesis
0.333
-
tetrahydrofolate
-
mutant R653Q
0.364
-
tetrahydrofolate
-
wild type
0.46
-
tetrahydrofolate
-
-
0.69
-
tetrahydrofolate
-
wild-type enzyme
0.8
-
tetrahydrofolate
-, Q83WS0
30C, pH 8.0
0.97
-
tetrahydrofolate
-
mutant enzyme H125S
1.12
-
tetrahydrofolate
-
mutant enzyme H131S
2.3
-
tetrahydrofolate
-
-
0.0055
-
tetrahydropteroyl-Glu2
-
-
0.029
-
tetrahydropteroyl-Glu2
-
-
0.0003
-
tetrahydropteroyl-Glu3
-
tetrahydropteroyl-Glu6
0.016
-
tetrahydropteroyl-Glu3
-
-
0.025
-
tetrahydropteroyl-Glu3
-
-
0.025
-
tetrahydropteroyl-Glu3
-
ATP, reaction with tetrahydropteroyl-Glu4
0.0001
-
tetrahydropteroyl-Glu4
-
tetrahydropteroyl-Glu5
0.003
-
tetrahydropteroyl-Glu5
-
-
0.59
-
MgATP2-
-
mutant enzyme H125S
additional information
-
additional information
-
effect of polyglutamate chain length of tetrahydropteroyl-(Glu)n on the Km values of formate and MgATP2-
-
additional information
-
additional information
-
monovalent cations decrease the Km for formate
-
additional information
-
additional information
-
-
-
additional information
-
additional information
-
Km-values for the forward reaction as a function of temperature in the presence and absence of NH4Cl
-
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
-
(6R,S)-tetrahydrofolate monoglutamate
-
above, recombinant enzyme, 30C
2.6
-
(6R,S)-tetrahydrofolate pteroylpentaglutamate
-
recombinant enzyme, 30C
10
-
(6R,S)-tetrahydrofolate pteroyltriglutamate
-
recombinant enzyme, 30C
0.39
-
ATP
-
27C, pH 7.0, R97S mutant FTHFS
0.99
-
ATP
-
27C, pH 7.0, wild-type FTHFS
6.08
-
ATP
-
27C, pH 7.0, wild-type FTHFS
0.4
-
formate
-
27C, pH 7.0, R97S mutant FTHFS
1.13
-
formate
-
27C, pH 7.0, wild-type FTHFS
6.08
-
formate
-
27C, pH 7.0, wild-type FTHFS
additional information
-
additional information
-
-
-
additional information
-
additional information
-
-
-
additional information
-
additional information
-
the Kcat/Km tetrahydrofolate values are 0.03 s/M for the monoglutamate and 0.71 s/M for the pentaglutatmate substrates
-
Ki VALUE [mM]
Ki VALUE [mM] Maximum
INHIBITOR
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.0338
-
ADP
-
mutant R653Q
0.0364
-
ADP
-
wild type enzyme
0.0296
-
pteroylpentaglutamate
-
wild type enzyme
0.0328
-
pteroylpentaglutamate
-
mutant R653Q
IC50 VALUE [mM]
IC50 VALUE [mM] Maximum
INHIBITOR
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.0033
-
(2S)-2-[[4-[(6aR)-3-amino-1,9-dioxo-5,6,6a,7-tetrahydro-4H-imidazol[3,4-f]pteridin-8-yl]benzoyl]amino]pentanedioate
-
dhch1-/pXNG4-FTL mutant, FV1 line
0.0037
-
(2S)-2-[[4-[(6aR)-3-amino-1,9-dioxo-5,6,6a,7-tetrahydro-4H-imidazol[3,4-f]pteridin-8-yl]benzoyl]amino]pentanedioate
-
WT/pXNG4-FTL mutant, FV1 line
0.00054
-
2,4-diamino-6-(3,4-dichlorophenoxy)-quinazoline
-
dhch1-/pXNG4-FTL mutant, FV1 line
0.00042
-
2,4-diamino-6-benzyl-5-(3-phenylpropyl)-pyrimidine
-
dhch1-/pXNG4-FTL mutant, FV1 line
0.00004
-
methotrexate
-
dhch1-/pXNG4-FTL mutant, FV1 line
SPECIFIC ACTIVITY [µmol/min/mg]
SPECIFIC ACTIVITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
23
-
-
synthetase activity of the wild type enzyme
23.8
-
-
synthetase activity of the mutant R653Q
40
-
-
-
780
-
P21164
recombinant FTHFS
additional information
-
-
-
additional information
-
-
-
additional information
-
Q8R013
mitochondrial isozyme activity in different cell lines, overview
additional information
-
-
100.2% activity of mutant R653Q after heating at 42C for 90 min, in 7.5% glycerol and 0.35 mM folate pentaglutamate; 102% activity of wild type enzyme after heating at 42C for 90 min, in 7.5% glycerol and 0.35 mM folate pentaglutamate; 57.4% activity of mutant R653Q, without adding of any cofactor, after heating at 42C for 90 min, in 7.5% glycerol; 72.3% activity of wild type enzyme, without adding of any cofactor, after heating at 42C for 90 min, in 7.5% glycerol; 80.5% activity of mutant R653Q after heating at 42C for 90 min, in 7.5% glycerol, 1.2 mM MgCl, 0.6 mM ATP; 88.2% activity of wild type enzyme after heating at 42C for 90 min, in 7.5% glycerol, 1.2 mM MgCl, 0.6 mM ATP; enzyme knock-out cells are transfected with either wild type or R653Q mutant and their ability to synthesize purines is assessed by a 14C-formate incorporation assay, the cells expressing the R653Q variant incorporate only 74% of wild-type levels of formate into DNA, the R653Q protein appears to have a significant impact on cellular nucleotide metabolism
additional information
-
-
MTHFD1L is upregulated in colon adeno-carcinomas; overexpression of MTHFD1L in HEK-292 cells stimulates colony formation indicating that expression of this gene confers a growth advantage
pH OPTIMUM
pH MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
7.5
-
-
-
TEMPERATURE OPTIMUM
TEMPERATURE OPTIMUM MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
27
-
-
assay at
30
-
-
-
30
-
-
assay at
SOURCE TISSUE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
SOURCE
Q6UB35
high transcript levels
Manually annotated by BRENDA team
Q6UB35
higher expression level
Manually annotated by BRENDA team
Q6UB35
2fold increased expression of gene DKFZp586G1517 compared to normal colon tissue
Manually annotated by BRENDA team
Q3V3R1
the MTHFD1L transcript is detected at all stages of mouse embryogenesis examined. MTHFD1L is expressed ubiquitously throughout the embryo but with localized regions of higher expression. The spatial pattern of MTHFD1L expression is virtually indistinguishable from that of MTHFD2 and cytoplasmic C1-THF synthase MTHFD1 in embryonic day 9.5 mouse embryos
Manually annotated by BRENDA team
Q6UB35
low expression level
Manually annotated by BRENDA team
Q8R013
; SF6 cell, immortalized fibroblast with disrupted gene encoding the trifunctional cytosolic DCS
Manually annotated by BRENDA team
Q3V3R1
embryonic fibroblast cell line
Manually annotated by BRENDA team
-
low expression
Manually annotated by BRENDA team
Pigeon
-
-
Manually annotated by BRENDA team
Q6UB35
low transcript levels
Manually annotated by BRENDA team
Q6UB35
higher expression level
Manually annotated by BRENDA team
Q6UB35
low expression level
Manually annotated by BRENDA team
-
low expression
Manually annotated by BRENDA team
Q6UB35
high expression level
Manually annotated by BRENDA team
Q6UB35
high transcript levels
Manually annotated by BRENDA team
Q6UB35
low transcript levels
Manually annotated by BRENDA team
Q6UB35
low expression level
Manually annotated by BRENDA team
Q6UB35
higher expression level
Manually annotated by BRENDA team
Q6UB35
high transcript levels
Manually annotated by BRENDA team
-
low expression
Manually annotated by BRENDA team
additional information
Q8R013
isozyme expression analysis and growth rates of cell lines, overview
Manually annotated by BRENDA team
additional information
-
the cytoplasmatic MTHFD1 is ubiquitously expressed in all mammalian cells
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
Q8R013
trifunctional cytosolic isozyme
Manually annotated by BRENDA team
-
mitochondrial isozyme
Manually annotated by BRENDA team
Q6UB35
mitochondrial isozyme, contains an N-terminal mitochondrial targeting sequence
Manually annotated by BRENDA team
Q8R013
mitochondrial monofunctional isozyme
Manually annotated by BRENDA team
-
mitochondrial C1-THF synthase behaves as a peripheral membrane protein, tightly associated with the matrix side of the mitochondrial inner membrane
Manually annotated by BRENDA team
Q3V3R1
MTHFD1L enzyme is present in mitochondria from normal embryonic tissues and embryonic fibroblast cell lines, and embryonic mitochondria possess the ability to synthesize formate from glycine. Greater than 75% of 1-C units entering the cytoplasmic methyl cycle are mitochondrially derived
Manually annotated by BRENDA team
PDB
SCOP
CATH
ORGANISM
Moorella thermoacetica (strain ATCC 39073)
Moorella thermoacetica (strain ATCC 39073)
Moorella thermoacetica (strain ATCC 39073)
Moorella thermoacetica (strain ATCC 39073)
Moorella thermoacetica (strain ATCC 39073)
Moorella thermoacetica (strain ATCC 39073)
Moorella thermoacetica (strain ATCC 39073)
Moorella thermoacetica (strain ATCC 39073)
Thermotoga maritima (strain ATCC 43589 / MSB8 / DSM 3109 / JCM 10099)
MOLECULAR WEIGHT
MOLECULAR WEIGHT MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
35000
-
-
recombinant short isoform, SDS-PAGE
107000
-
-
recombinant mitochondrial C1-THF synthase without the presequence but with the V5 epitope tag, SDS-PAGE
110000
-
-
gel filtration
130000
-
-
gel filtration
143000
-
-
recombinant mitochondrial isozyme, gel filtration
150000
-
-
gel filtration
201000
-
-
gel filtration
226000
-
-
gel filtration
240000
-
-
gel filtration, sedimentation analysis
240000
-
-, Q83WS0
gel filtration
SUBUNITS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
?
-
x * 67727, SDS-PAGE
?
-
x * 59983, calculation from nucleotide sequence
dimer
-
2 * 67000, SDS-PAGE
dimer
-
2 * 56000, SDS-PAGE
dimer
-
2 * 102000, homodimer, sequence calculation
tetramer
-
in the presence of specific monovalent cations, K+, Cs+, or NH4+, inactive monomers of formyltetrahydrofolate synthetase associate to a catalytically active tetramer
tetramer
Clostridium acidi-urici, Clostridium cylindrosporum
-
enzymes exist as a catalytically active tetramer in the presence of specific monovalent cations or as an inactive monomer in their absence
tetramer
P21164
4 * 60000, SDS-PAGE
tetramer
-, Q83WS0
4 * 60000, SDS-PAGE
dimer
-
by gel filtration
additional information
-
a tryptic fragment that contains 10-formyltetrahydrofolate synthetase activity is a dimer, MW 66000
Crystallization/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
-
Clostridium acidi-urici
-
crystals of FTHFS complexed with NH4+, K+ or Cs+ are grown by vapor diffusion from 46% saturated ammonium sulfate, 1 mM dithiothreitol and 1% polyehtylene glycol 1000 in 50 mM potassium maleate buffer, pH 7.6, crystals diffract to 3.0-3.2 A resolution
P21164
Se-Met FTHFS is crystallized by hanging-drop vapor-diffusion, crystals diffract to 2.5 A
P21164
pH STABILITY
pH STABILITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
6.5
9
-
unstable below pH 6.5 and above pH 9.0
TEMPERATURE STABILITY
TEMPERATURE STABILITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
23
-
-
,the large domain of the multifuncional enzyme, that contains the active site for the 10-formyltetrahydrofolate synthetase is more stable at 23C than at 0C
47
-
-
transition at 47C is due to the denaturation of a domain which binds MgATP2- and contains the synthetase active site
69
-
P21164
in the absence of monovalent cation
70
-
-
10 min stable
70
-
-
rapid inactivation in absence of NH4Cl. In presence of 50 mM NH4Cl, about 50% loss of activity after 15 min and no more loss of activity thereafter
75
-
-
rapid denaturation
79
-
P21164
in the presence of 200 mM K+
additional information
-
-
the binding of tetrahydropteroylpolyglutamate, MgATP2-, and NH4+ increases the denaturation temperature by 12C and abolishes the cold lability of the enzyme
additional information
-
-
NH4+ and K+, but not Na+ increase the thermostability
additional information
-
-
thermolability is reduced by magnesium adenosine triphosphate and eliminated by the substrate analog folate pentaglutamate, suggesting that folate status may modulate impact of the variant R653Q
GENERAL STABILITY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
photooxidation in presence of methylene blue results in a pseudo-first order loss of enzymatic activity and destruction of histidine residues
Clostridium acidi-urici
-
addition of monovalent cations to the dissociated enzyme causes the inactive monomers to reassociate to the active tetramer. The order of cation effectiveness is NH4+ > Tl+ > Rb+ ~ K+ > Cs+ > Na+ ~ Li+. The rate and extent of reactivation is influenced by the counter ion: sulfate and phosphate stimulate reassociation, thiocyanate, trichloroacetate, and perchlorate completly inhibit reassociation. The extent of reactivation is dependent upon protein concentration. The optimum protein concentration depends on the pH at which reactivation is performed
-
purified enzyme as crystalline suspension, 15% loss of activity after 1 month
-
tetramer is stabilized by 0.1 M sulfate in absence of an active monovalent cation
-
unstable in absence of monovalent cations
-
unstable in presence of urea and guanidinium chloride
-
K+ or NH4+ increase stability of the large domain of the multifuncional enzyme, that contains the active site for the 10-formyltetrahydrofolate synthetase
-
the binding of tetrahydropteroylpolyglutamate, MgATP2-, and NH4+ alters the susceptibility to digestion by chymotrypsin
-
enzyme is unstable in phosphate buffers in the absence of high concentrations of salt
-
STORAGE STABILITY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
4C, in presence of PMSF, minimal loss of activity after several months
-
Purification/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
-
Clostridium acidi-urici
-
by anion-exchange chromatography
-
recombinant enzyme is partially purified from HEK-293 cells by subcellular fractionation
Q6UB35
recombinant maltose-binding protein fusion mitochondrial isozyme from Escherichia coli by metal affinity chromatography and gel filtration, the MBP-tag is cleaved off by TEV protease
-
TALON cobalt metal affinity resin chromatography
-
ammonium sulfate, Phenyl Sepharose, Source15Q, hydroxyapatite, Resource Q
-, Q83WS0
recombinant FTHFS
-
recombinant FTHFS, heparin Agarose, Phenyl Sepharose
P21164
TALON cobalt metal affinity resin chromatography
-
large-scale purification
-
Cloned/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
gene FTHFS, DNA and amino acid sequence determination and analysis, phylogenetic analysis, genetic clusters, overview. Cloning and expression in Escherichia coli
-
gene fths, DNA and amino acid sequence determination and analysis, quantitative expression analysis by real-time PCR, phylogenetic analysis, cloning and expression in Escherichia coli strain JM109
Q15K82
gene fths, DNA and amino acid sequence determination and analysis, quantitative expression analysis by real-time PCR, phylogenetic analysis, cloning and expression in Escherichia coli strain JM109
Q8GMP9
gene FTHFS, DNA and amino acid sequence determination and analysis, phylogenetic analysis, genetic clusters, overview. Cloning and expression in Escherichia coli
Q9AHS2
gene fths, DNA and amino acid sequence determination and analysis, quantitative expression analysis by real-time PCR, phylogenetic analysis, cloning and expression in Escherichia coli strain JM109
Q9AHS2
gene fths, DNA and amino acid sequence determination and analysis, quantitative expression analysis by real-time PCR, phylogenetic analysis, cloning and expression in Escherichia coli strain JM109
Q9AHR6
gene FTHFS, DNA and amino acid sequence determination and analysis, phylogenetic analysis, genetic clusters, overview. Cloning and expression in Escherichia coli
-
gene fths, DNA and amino acid sequence determination and analysis, quantitative expression analysis by real-time PCR, phylogenetic analysis, cloning and expression in Escherichia coli strain JM109
Q8R7L3
gene fths, DNA and amino acid sequence determination and analysis, quantitative expression analysis by real-time PCR, phylogenetic analysis, cloning and expression in Escherichia coli strain JM109
Q9AHR8
-
Clostridium acidi-urici
-
gene fths, DNA and amino acid sequence determination and analysis, quantitative expression analysis by real-time PCR, phylogenetic analysis, cloning and expression in Escherichia coli strain JM109
P13419
expression in Escherichia coli
-
gene fths, DNA and amino acid sequence determination and analysis, quantitative expression analysis by real-time PCR, phylogenetic analysis, cloning and expression in Escherichia coli strain JM109
Q9AHS1
gene FTHFS, DNA and amino acid sequence determination and analysis, phylogenetic analysis, genetic clusters, overview. Cloning and expression in Escherichia coli
-
gene fths, DNA and amino acid sequence determination and analysis, quantitative expression analysis by real-time PCR, phylogenetic analysis, cloning and expression in Escherichia coli strain JM109
-
gene FTHFS, DNA and amino acid sequence determination and analysis, phylogenetic analysis, genetic clusters, overview. Cloning and expression in Escherichia coli
-
gene fths, DNA and amino acid sequence determination and analysis, quantitative expression analysis by real-time PCR, phylogenetic analysis, cloning and expression in Escherichia coli strain JM109
-
gene fths, DNA and amino acid sequence determination and analysis, quantitative expression analysis by real-time PCR, phylogenetic analysis, cloning and expression in Escherichia coli strain JM109; gene fths, DNA and amino acid sequence determination and analysis, quantitative expression analysis by real-time PCR, phylogenetic analysis, cloning and expression in Escherichia coli strain JM109
Q8GJ02, Q9AHR7
gene FTHFS, DNA and amino acid sequence determination and analysis, phylogenetic analysis, genetic clusters, overview. Cloning and expression in Escherichia coli
-
expressed in CHO cells and Escherichia coli
-
expressed in Escherichia coli
-
expression in CHO cells and Saccharomyces cerevisiae
Q6UB35
expression in Escherichia coli, localization of the interdomain region of the trifunctional enzyme by site-directed mutagenesis
-
expression of the mitochondrial isozyme as maltose-binding protein fusion protein in Escherichia coli, overexpression in yeast
-
gene DKFZp586G1517, DNA and amino acid sequence determination and analysis, overexpression of mitochondrial enzyme in HEK-293 cells, unlabeled or FLAG-tagged, stimulates cell growth
Q6UB35
the wild type and R653Q mutant pBKeDCS constructs are transformed into Escherichia coli BL21 DE3 to express the full-length protein
-
overexpression of FTL using the multicopy episomal vector pXNG4-FTL
-
gene fths, DNA and amino acid sequence determination and analysis, quantitative expression analysis by real-time PCR, phylogenetic analysis, cloning and expression in Escherichia coli strain JM109
Mesorhizobium loti, Mesorhizobium sp.
-
expression in Escherichia coli
-
gene fths, DNA and amino acid sequence determination and analysis, quantitative expression analysis by real-time PCR, phylogenetic analysis, cloning and expression in Escherichia coli strain JM109
P21164
DNA sequence determination and analysis
Q8R013
gene FTHFS, DNA and amino acid sequence determination and analysis, phylogenetic analysis, genetic clusters, overview. Cloning and expression in Escherichia coli
-
expressed in CHO cells and Escherichia coli
-
gene fths, DNA and amino acid sequence determination and analysis, quantitative expression analysis by real-time PCR, phylogenetic analysis, cloning and expression in Escherichia coli strain JM109
-
deletion of the MIS1 gene has little effect
P05440, P07245
gene fths, DNA and amino acid sequence determination and analysis, quantitative expression analysis by real-time PCR, phylogenetic analysis, cloning and expression in Escherichia coli strain JM109
-
gene FTHFS, DNA and amino acid sequence determination and analysis, phylogenetic analysis, genetic clusters, overview. Cloning and expression in Escherichia coli
-
gene fths, DNA and amino acid sequence determination and analysis, quantitative expression analysis by real-time PCR, phylogenetic analysis, cloning and expression in Escherichia coli strain JM109
Q9AHR5
gene fths, DNA and amino acid sequence determination and analysis, quantitative expression analysis by real-time PCR, phylogenetic analysis, cloning and expression in Escherichia coli strain JM109
Q9AHR4
gene fths, DNA and amino acid sequence determination and analysis, quantitative expression analysis by real-time PCR, phylogenetic analysis, cloning and expression in Escherichia coli strain JM109
Q9AHR9
gene fths, DNA and amino acid sequence determination and analysis, quantitative expression analysis by real-time PCR, phylogenetic analysis, cloning and expression in Escherichia coli strain JM109
Q9HI67
gene fths, DNA and amino acid sequence determination and analysis, quantitative expression analysis by real-time PCR, phylogenetic analysis, cloning and expression in Escherichia coli strain JM109
-
gene fths, DNA and amino acid sequence determination and analysis, quantitative expression analysis by real-time PCR, phylogenetic analysis, cloning and expression in Escherichia coli strain JM109
Q8GIN9
ENGINEERING
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
H125S
-
site-directed mutant enzymes H125S, H131S, and H268S do not fold properly and/or do not associate to the active tetramer and, as a consequence are susceptible to intracellular proteolytic digestion
H131S
-
site-directed mutant enzymes H125S, H131S, and H268S do not fold properly and/or do not associate to the active tetramer and, as a consequence are susceptible to intracellular proteolytic digestion
H268S
-
site-directed mutant enzymes H125S, H131S, and H268S do not fold properly and/or do not associate to the active tetramer and, as a consequence are susceptible to intracellular proteolytic digestion
R653Q
-
amino position 653 is located within the 10-formyltetrahydrofolate synthetase domain of the MTHFD1 protein affecting the supply of 10-formyltetrahydrofolate required for purine synthesis
R653Q
-
mutant enzyme has normal substrate affinity but a 36% reduction in half-life at 42C, the mutation reduces the metabolic activity of MTHFD1 within cells: formate incorporation into DNA in murine Mthfd1 knockout cells transfected with Arg653Gln is reduced by 26%, compared to cells transfected with wild-type protein, the mutant may increase the risk for neural tube defects, under ideal storage and standard assay conditions, the synthetase activity of MTHFD1 is unaffected by the R653Q mutation
E98D
P21164
36% of wild-type activity
E98Q
P21164
93% of wild-type activity, slight increase in thermal stability in the absence of monovalent cation
E98S
P21164
61% of wild-type activity
R97E
-
no activity
G1958A
-
the mutation is not associated with depression in postmenopausal women
additional information
-
the recombinant protein product (short isoform) of the alternatively spliced short transcript of the mitochondrial isozyme is not enzymatically active
R97S
-
35% of wild-type kcat
additional information
Q8R013
construction of a DCS disruption knockout mutant fibroblast SF6 cell line lacking the cytoplasmic isozyme but expressing active mitochondrial isozyme from a disruption mutant embryonic stem cell line
additional information
-
the recombinant protein product (short isoform) of the alternatively spliced short transcript of the mitochondrial isozyme is not enzymatically active
Renatured/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
enzymes denatured in 6 M urea and 4 M guanidinium chloride refold upon dilution of the denaturant-protein solution to give final concentrations of 0.5 M urea or 0.1 M guanidinium chloride. In presence of NH4+, but not in its absence the refolded proteins associate to produce the catalytically active tetramer. 80% of the enzymatic acitivity is recovered
Clostridium acidi-urici, Clostridium cylindrosporum
-
APPLICATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
pharmacology
Q6UB35
the enzyme might be a target for colorectal cancer therapy