Information on EC 1.5.1.6 - formyltetrahydrofolate dehydrogenase

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The expected taxonomic range for this enzyme is: Euteleostomi

EC NUMBER
COMMENTARY
1.5.1.6
-
RECOMMENDED NAME
GeneOntology No.
formyltetrahydrofolate dehydrogenase
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
10-formyltetrahydrofolate + NADP+ + H2O = tetrahydrofolate + CO2 + NADPH + H+
show the reaction diagram
sequential mechanism of substrate addition
-
10-formyltetrahydrofolate + NADP+ + H2O = tetrahydrofolate + CO2 + NADPH + H+
show the reaction diagram
reaction mechanism
-
10-formyltetrahydrofolate + NADP+ + H2O = tetrahydrofolate + CO2 + NADPH + H+
show the reaction diagram
FDH catalyzes the hydrolytic cleavage of the formyl group in the N-terminal catalytic domain, followed by NADP+-dependent oxidation of the formyl group toCO2 in the C-terminal aldehyde dehydrogenase domain
-
10-formyltetrahydrofolate + NADP+ + H2O = tetrahydrofolate + CO2 + NADPH + H+
show the reaction diagram
-
-
-
-
REACTION TYPE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
oxidation
-
-
-
-
oxidation
-
-
redox reaction
-
-
-
-
redox reaction
-
-
reduction
-
-
-
-
PATHWAY
KEGG Link
MetaCyc Link
One carbon pool by folate
-
SYSTEMATIC NAME
IUBMB Comments
10-formyltetrahydrofolate:NADP+ oxidoreductase
-
SYNONYMS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
10-FDH
-
-
-
-
10-formyl tetrahydrofolate:NADP oxidoreductase
-
-
-
-
10-formyl-H2PtGlu:NADP oxidoreductase
-
-
-
-
10-formyl-H4folate dehydrogenase
-
-
-
-
10-formyltetrahydrofolate dehydrogenase
-
-
-
-
10-formyltetrahydrofolate dehydrogenase
-
-
10-formyltetrahydrofolate dehydrogenase
-
-
10-formyltetrahydrofolate dehydrogenase
P28037
-
10-formyltetrahydrofolate dehydrogenase
Q5HZB2
-
10-fTHF dehydrogenase
-
-
10-FTHFDH
-
-
-
-
ALDH1L2
-
gene name
ALDH1L2
O75891, Q3SY69
-
dehydrogenase, formyltetrahydrofolate
-
-
-
-
FBP-CI
-
-
-
-
FBP-CI proteins
-
-
-
-
FDH
-
-
-
-
FDH
-
the enzyme has also hydrolase and aldehyde dehydrogenase activities
FDH
P28037
-
mtFDH
-
mitochondrial isoform
N10-formyltetrahydrofolate dehydrogenase
-
-
-
-
proteins, folate-binding, cytosol I
-
-
-
-
folate-binding proteins, cytosol I
-
-
-
-
additional information
-
identical with folate binding protein cytosol-I, FBP-CI
additional information
-
identical with protein-arginine methyltransferase from liver cytosol, EC 2.1.1.23
CAS REGISTRY NUMBER
COMMENTARY
37256-25-0
-
GENERAL INFORMATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
physiological function
-
FDH induces apoptosis in PC-3 prostate cells through simultaneous activation of the c-Jun-NH2-kinase JNK and extracellular signal-regulated kinase ERK pathways with JNK phosphorylating c-Jun and ERK1/2 phosphorylating Elk-1. The JNK1/2 inhibitor SP600125 or ERK1/2 inhibitor PD98059 prevents phosphorylation of c-Jun and Elk-1, correspondingly and partially protects PC-3 cells from FDH-induced cytotoxicity. Combination of the two inhibitors produces an additive effect. The FDH-induced apoptosis in p53-proficient A-549 cells also proceeds through activation of JNK1/2, but the down-stream target for JNK2 is p53 instead of c-Jun. In A-549 cells, FDH activates caspase 9, whereas in PC-3 cells, it activates caspase 8
SUBSTRATE
PRODUCT                      
REACTION DIAGRAM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
10-formyl-5,8-dideazafolate + NADP+ + H2O
5,8-dideazafolate + CO2 + NADPH + H+
show the reaction diagram
-
-
-
?
10-formyl-5,8-dideazafolate + NADP+ + H2O
5,8-dideazafolate + CO2 + NADPH + H+
show the reaction diagram
-
-
-
?
10-formyl-5,8-dideazafolate + NADP+ + H2O
5,8-dideazafolate + CO2 + NADPH + H+
show the reaction diagram
-
-
-
?
10-formyl-5,8-dideazafolate + NADP+ + H2O
5,8-dideazafolate + CO2 + NADPH + H+
show the reaction diagram
-
-
-
-
10-formyl-5,8-dideazafolate + NADP+ + H2O
5,8-dideazafolate + CO2 + NADPH + H+
show the reaction diagram
-
good substrate
-
?
10-formyl-5,8-dideazafolate + NADP+ + H2O
5,8-dideazafolate + CO2 + NADPH + H+
show the reaction diagram
-
good substrate
-
ir
10-formyl-5,8-dideazafolate + NADP+ + H2O
5,8-dideazafolate + CO2 + NADPH + H+
show the reaction diagram
-
stable synthetic analogue can substitute for the labile natural substrate, affinity is twice as high as for 10-formyltetrahydrofolate
-
?
10-formyl-5,8-dideazafolate tetraglutamate + NADP+ + H2O
5,8-dideazafolate tetraglutamate + CO2 + NADPH + H+
show the reaction diagram
-
-
tightly bound product
ir
10-formyltetrahydrofolate + NADP+ + H2O
tetrahydrofolate + CO2 + NADPH + H+
show the reaction diagram
-
-
-
?
10-formyltetrahydrofolate + NADP+ + H2O
tetrahydrofolate + CO2 + NADPH + H+
show the reaction diagram
-
-
-
?
10-formyltetrahydrofolate + NADP+ + H2O
tetrahydrofolate + CO2 + NADPH + H+
show the reaction diagram
-
-
-
?
10-formyltetrahydrofolate + NADP+ + H2O
tetrahydrofolate + CO2 + NADPH + H+
show the reaction diagram
-
-
-
-
?
10-formyltetrahydrofolate + NADP+ + H2O
tetrahydrofolate + CO2 + NADPH + H+
show the reaction diagram
-
-
-
?
10-formyltetrahydrofolate + NADP+ + H2O
tetrahydrofolate + CO2 + NADPH + H+
show the reaction diagram
-
-
-
?
10-formyltetrahydrofolate + NADP+ + H2O
tetrahydrofolate + CO2 + NADPH + H+
show the reaction diagram
-
-
-
?
10-formyltetrahydrofolate + NADP+ + H2O
tetrahydrofolate + CO2 + NADPH + H+
show the reaction diagram
-
-
-
?
10-formyltetrahydrofolate + NADP+ + H2O
tetrahydrofolate + CO2 + NADPH + H+
show the reaction diagram
-
-
-
?
10-formyltetrahydrofolate + NADP+ + H2O
tetrahydrofolate + CO2 + NADPH + H+
show the reaction diagram
-
-
-
?
10-formyltetrahydrofolate + NADP+ + H2O
tetrahydrofolate + CO2 + NADPH + H+
show the reaction diagram
-
-
-
-
?
10-formyltetrahydrofolate + NADP+ + H2O
tetrahydrofolate + CO2 + NADPH + H+
show the reaction diagram
-
-
-
?
10-formyltetrahydrofolate + NADP+ + H2O
tetrahydrofolate + CO2 + NADPH + H+
show the reaction diagram
-
-
-
?
10-formyltetrahydrofolate + NADP+ + H2O
tetrahydrofolate + CO2 + NADPH + H+
show the reaction diagram
-
-
-
ir
10-formyltetrahydrofolate + NADP+ + H2O
tetrahydrofolate + CO2 + NADPH + H+
show the reaction diagram
E3NZ06
-
-
-
?
10-formyltetrahydrofolate + NADP+ + H2O
tetrahydrofolate + CO2 + NADPH + H+
show the reaction diagram
-
-
very tight binding of product, binds its product rather than its substrate
?
10-formyltetrahydrofolate + NADP+ + H2O
tetrahydrofolate + CO2 + NADPH + H+
show the reaction diagram
-
-
very tight binding of product, binds its product rather than its substrate
?
10-formyltetrahydrofolate + NADP+ + H2O
tetrahydrofolate + CO2 + NADPH + H+
show the reaction diagram
-
natural substrate
-
?
10-formyltetrahydrofolate + NADP+ + H2O
tetrahydrofolate + CO2 + NADPH + H+
show the reaction diagram
-
Asp-142 is an essential residue in enzyme mechanism, it influences folate binding, model of substrate binding pocket
-
?
10-formyltetrahydrofolate + NADP+ + H2O
tetrahydrofolate + CO2 + NADPH + H+
show the reaction diagram
-
His-106 is involved in enzyme catalysis and in folding of the N-terminal domain, enzyme requires Cys-707 for catalysis, which is located inside the C-terminal domain, mechanism includes hydrolase reaction as essential part
-
?
10-formyltetrahydrofolate + NADP+ + H2O
tetrahydrofolate + CO2 + NADPH + H+
show the reaction diagram
-
structure of enzyme domains and of catalytic centers
-
?
10-formyltetrahydrofolate + NADP+ + H2O
tetrahydrofolate + CO2 + NADPH + H+
show the reaction diagram
-
structure of enzyme domains and of catalytic centers
high affinity for tetrahydrofolate
?
10-formyltetrahydrofolate + NADP+ + H2O
tetrahydrofolate + CO2 + NADPH + H+
show the reaction diagram
-
Cys-707 is involved in enzyme activity
-
?
10-formyltetrahydrofolate + NADP+ + H2O
tetrahydrofolate + CO2 + NADPH + H+
show the reaction diagram
-
Cys-707 is a key residue of the dehydrogenase active site and acts as nucleophile in the formation of an enzyme-linked thiohemiacetal intermediate
-
?
10-formyltetrahydrofolate + NADP+ + H2O
tetrahydrofolate + CO2 + NADPH + H+
show the reaction diagram
-
10-formyltetrahydrofolate is associated with enzyme when it is rapidly isolated, after storage for 24 h before separation of the binding proteins there remains none and tetrahydrofolate is the predominant form bound to enzyme because of the hydrolase activity
very tight binding of product, binds its product rather than its substrate
?
10-formyltetrahydrofolate + NADP+ + H2O
tetrahydrofolate + CO2 + NADPH + H+
show the reaction diagram
-
specific for NADP+
-
-
10-formyltetrahydrofolate + NADP+ + H2O
tetrahydrofolate + CO2 + NADPH + H+
show the reaction diagram
-
specific for NADP+
-
?
10-formyltetrahydrofolate + NADP+ + H2O
tetrahydrofolate + CO2 + NADPH + H+
show the reaction diagram
-
specific for NADP+
-
?
10-formyltetrahydrofolate + NADP+ + H2O
tetrahydrofolate + CO2 + NADPH + H+
show the reaction diagram
-
specific for NADP+
-
?
10-formyltetrahydrofolate + NADP+ + H2O
tetrahydrofolate + CO2 + NADPH + H+
show the reaction diagram
-
specific for NADP+
-
?
10-formyltetrahydrofolate + NADP+ + H2O
tetrahydrofolate + CO2 + NADPH + H+
show the reaction diagram
-
specific for NADP+
-
?
10-formyltetrahydrofolate + NADP+ + H2O
tetrahydrofolate + CO2 + NADPH + H+
show the reaction diagram
-
specific for NADP+, calculated equilibrium constant: 160000000, specific for (-)-10-formyltetrahydrofolate and NADP+
-
ir
10-formyltetrahydrofolate + NADP+ + H2O
tetrahydrofolate + CO2 + NADPH + H+
show the reaction diagram
-
enzyme requires Cys-707 to form a thiohemiacetal with the formyl group of 10-formyltetrahydrofolate
high affinity for tetrahydrofolate
?
10-formyltetrahydrofolate + NADP+ + H2O
tetrahydrofolate + CO2 + NADPH + H+
show the reaction diagram
-
mechanism which proceeds through thiohemiacetal and thioester intermediates, nucleophilic attack by the essential active site Cys-707 on the carbonyl group of 10-formyltetrahydrofolate, folate binding domain requires presence of an intact ring system
-
?
10-formyltetrahydrofolate + NADP+ + H2O
tetrahydrofolate + CO2 + NADPH + H+
show the reaction diagram
-
enzyme binds one molecule of tetrahydrofolate and two molecules of NADP+ per tetramer, tetrahydrofolate and NADP+ bind to separate domains, higher affinity for NADP+ at lower enzyme concentrations
high affinity for tetrahydrofolate
?
10-formyltetrahydrofolate + NADP+ + H2O
tetrahydrofolate + CO2 + NADPH + H+
show the reaction diagram
-
recycling of excess 10-formyltetrahydrofolate that is not needed for purine biosynthesis and restoration of the tetrahydrofolate pool, important for formate metabolism by clearing it as CO2 and thus protecting cells from formate intoxication
-
?
10-formyltetrahydrofolate + NADP+ + H2O
tetrahydrofolate + CO2 + NADPH + H+
show the reaction diagram
-
enzyme is an important factor in regulation of formate oxidation and is related with methanol poisoning
-
?
10-formyltetrahydrofolate + NADP+ + H2O
tetrahydrofolate + CO2 + NADPH + H+
show the reaction diagram
-
regulatory mechanism to control the in vivo folate pool size
-
?
10-formyltetrahydrofolate + NADP+ + H2O
tetrahydrofolate + CO2 + NADPH + H+
show the reaction diagram
-
disposal of excess one-carbon units, oxidation of one-carbon moieties is regulated by the ratio of formyltetrahydrofolate to tetrahydrofolate in liver, regulation of the proportion of folate present in the tetrahydrofolate form, presumably to make it available for other reactions of one-carbon metabolism
-
?
10-formyltetrahydrofolate + NADP+ + H2O
tetrahydrofolate + CO2 + NADPH + H+
show the reaction diagram
-
regulation of the ratio of 10-formyltetrahydrofolate to tetrahydrofolate in the cell in response to yet unknown aldehyde and thiol metabolites
-
?
10-formyltetrahydrofolate + NADP+ + H2O
tetrahydrofolate + CO2 + NADPH + H+
show the reaction diagram
-
a major liver enzyme, contributing to more than one metabolic pathway, regeneration of the tetrahydrofolate pool, not essential for viability
-
?
10-formyltetrahydrofolate + NADP+ + H2O
tetrahydrofolate + CO2 + NADPH + H+
show the reaction diagram
-
folate-dependent metabolism of formate to carbon dioxide
-
?
10-formyltetrahydrofolate + NADP+ + H2O
tetrahydrofolate + CO2 + NADPH + H+
show the reaction diagram
-
regulation of the ratio of 10-formyltetrahydrofolate to tetrahydrofolate and of the purine biosynthesis through control of the level of 10-formyltetrahydrofolate, down-regulation of FDH in tumors is one of the cellular mechanisms that enhance proliferation, FDH possesses tumor specific suppressor effects
-
?
10-formyltetrahydrofolate + NADP+ + H2O
tetrahydrofolate + CO2 + NADPH + H+
show the reaction diagram
-
major disposal route for excess one-carbon units produced in folate-mediated metabolism
-
?
10-formyltetrahydrofolate + NADP+ + H2O
tetrahydrofolate + CO2 + NADPH + H+
show the reaction diagram
-
folate-dependent pathway is the exclusive route of formate metabolism in primates, plays major role in disposition of formate generated from one-carbon moieties of environmental chemicals, drugs, and foods, importance in the toxicity of methanol
-
?
10-formyltetrahydrofolate + NADP+ + H2O
tetrahydrofolate + CO2 + NADPH + H+
show the reaction diagram
-
a major folate-binding protein of liver cytosol, 10-formyltetrahydrofolate polyglutamates are tightly bound in vivo
-
?
10-formyltetrahydrofolate + NADP+ + H2O
?
show the reaction diagram
-
the enzyme is composed of three domains and possesses three catalytic activities but has only two catalytic centers. The amino-terminal domain (residues 1-310) bears 10-formyltetrahydrofolate hydrolase activity, the carboxyl-terminal domain (residues 420-902) bears an aldehyde dehydrogenase activity, and the full-length FDH produces 10-formyltetrahydrofolate dehydrogenase activity
-
-
?
10-formyltetrahydropteroylhexaglutamate + NADP+ + H2O
tetrahydropteroylhexaglutamate + CO2 + NADPH
show the reaction diagram
-
-
-
?
10-formyltetrahydropteroylhexaglutamate + NADP+ + H2O
tetrahydropteroylhexaglutamate + CO2 + NADPH
show the reaction diagram
-
-
-
?
10-formyltetrahydropteroylpentaglutamate + NADP+ + H2O
tetrahydropteroylpentaglutamate + CO2 + NADPH
show the reaction diagram
-
-
-
?
10-formyltetrahydropteroylpentaglutamate + NADP+ + H2O
tetrahydropteroylpentaglutamate + CO2 + NADPH
show the reaction diagram
-
natural substrate
-
?
10-formyltetrahydropteroylpentaglutamate + NADP+ + H2O
tetrahydropteroylpentaglutamate + CO2 + NADPH
show the reaction diagram
-
product binds 60fold more tightly than the substrate, important site of binding of folylpolyglutamates in liver, regulation of the interconversion of 10-formyltetrahydropteroylpolyglutamate to tetrahydropteroylpolyglutamate and therefore of the high-energy formyl charge of the cell
-
ir
10-formyltetrahydropteroylpolyglutamate + NADP+ + H2O
tetrahydropteroylpolyglutamate + CO2 + NADPH + H+
show the reaction diagram
-
-
-
-
?
10-formyltetrahydropteroylpolyglutamate + NADP+ + H2O
tetrahydropteroylpolyglutamate + CO2 + NADPH + H+
show the reaction diagram
-
-
-
?
10-formyltetrahydropteroylpolyglutamate + NADP+ + H2O
tetrahydropteroylpolyglutamate + CO2 + NADPH + H+
show the reaction diagram
-
-
-
ir
10-formyltetrahydropteroylpolyglutamate + NADP+ + H2O
tetrahydropteroylpolyglutamate + CO2 + NADPH + H+
show the reaction diagram
-
affinity increases with increasing length of polyglutamyl chain
-
-
?
ATP + formate + tetrahydrofolate
ADP + phosphate + 10-formyltetrahydrofolate
show the reaction diagram
-
-
-
-
?
additional information
?
-
-
-
-
-
-
additional information
?
-
-
-
-
-
-
additional information
?
-
-
enzyme exhibit additional to 10-formyltetrahydrofolate dehydrogenase/hydrolase activities NADP+-dependent aldehyde dehydrogenase activity with propanal as preferred substrate
-
-
-
additional information
?
-
-
enzyme exhibit additional to 10-formyltetrahydrofolate dehydrogenase/hydrolase activities NADP+-dependent aldehyde dehydrogenase activity with propanal as preferred substrate
-
-
-
additional information
?
-
-
not as substrate: (+)-10-formyltetrahydrofolate
-
-
-
additional information
?
-
-
bifunctional enzyme: 10-formyltetrahydrofolate dehydrogenase separated from hydrolase activity, activities are functions of different active sites and take place simultaneously in presence of NADP+
-
-
-
additional information
?
-
-
hydrolysis at 25% of dehydrogenase activity, 10-formyltetrahydrofolate dehydrogenase/hydrolase activities occur at the same time and are associated with separate active sites
-
-
-
additional information
?
-
-
10-formyltetrahydrofolate dehydrogenase/hydrolase activities occur at the same time and are associated with separate active sites
-
-
-
additional information
?
-
-
enzyme catalyzes also NADP+-independent hydrolytic cleavage of 10-formyltetrahydrofolate to tetrahydrofolate and formate, hydrolysis is very inefficient compared to dehydrogenase reaction and may be an artifact of assay system
-
-
-
additional information
?
-
-
bifunctional enzyme: NADP+-dependent dehydrogenase activity and NADP+-independent hydrolase activity of 10-formyltetrahydrofolate with two active sites
-
-
-
additional information
?
-
-
10-formyltetrahydrofolate dehydrogenase and hydrolase are closely related and separately compartmentalized enzymes
-
-
-
additional information
?
-
-
2fold higher 10-formyltetrahydrofolate dehydrogenase than hydrolase activity, hydrolase and dehydrogenase catalytic centers are overlapping
-
-
-
additional information
?
-
-
irreversible covalent linkage of 5-formyltetrahydrofolate to enzyme, 2 mol bound per mol of enzyme monomer, 5-formyltetrahydrofolate is not the natural substrate and arises from 10-formyltetrahydrofolate
-
-
-
additional information
?
-
-
310 amino acid residue N-terminal domain has 10-formyltetrahydrofolate hydrolase activity and substrate binding site, C-terminal domain has aldehyde dehydrogenase activity and is used as catalytic center in dehydrogenase reaction, full-length enzyme is required for 10-formyltetrahydrofolate dehydrogenase activity, the two domains work in concert
-
-
-
additional information
?
-
-
enzyme consists of two independent folded domains connected by a linker sequence: a 32 kDa N-terminal domain with 10-formyltetrahydrofolate binding site shows hydrolase activity and a 63 kDa C-terminal domain with NADP+ binding site and Cys-707 shows aldehyde dehydrogenase activity, native structure of enzyme is necessary for 10-formyltetrahydrofolate dehydrogenase activity
-
-
-
additional information
?
-
-
FDH has also methyltransferase activity
-
-
-
additional information
?
-
-
not as substrate: 5-formyltetrahydrofolate
-
-
-
additional information
?
-
-
enzyme catalyzes hydrolytic cleavage of 10-formyltetrahydrofolate to formate and tetrahydrofolate in absence of NADP+ (15-30% of the rate of oxidative reaction)
-
-
-
additional information
?
-
-
bifunctional protein: 10-formyltetrahydrofolate dehydrogenase/hydrolase, hydrolysis at 20-30% of the oxidative rate
-
-
-
additional information
?
-
-
hydrolysis catalyzed by enzyme at 21% of the rate of CO2 formation
-
-
-
additional information
?
-
-
enzyme functions not as an aldehyde dehydrogenase in vivo, 10-formyltetrahydrofolate hydrolase activity is of no physiological significance, disulfiram may inhibit enzyme activity and probably perturb hepatic folate metabolism in vivo
-
-
-
additional information
?
-
-
FDH-expressing cells show accumulation of cells in G0-G1 phase and a sharp decrease of cells in S phase. Accumulation of the tumor suppressor protein p53 and its downstream target p21. FDH antiproliferative effects on A549 cells include both G1 cell cycle arrest and caspase-dependent apoptosis
-
-
-
additional information
?
-
-
activation of p53 tumor suppressor protein-dependent pathways is a general downstream mechanism in response to induction of enzyme expression in p53 functional cancer cells
-
-
-
additional information
?
-
E3NZ06
enzyme does not catalyze the oxidation of 10-formyltetrahydrofolate or propanal
-
-
-
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
10-formyltetrahydrofolate + NADP+ + H2O
tetrahydrofolate + CO2 + NADPH + H+
show the reaction diagram
-
-
-
-
?
10-formyltetrahydrofolate + NADP+ + H2O
tetrahydrofolate + CO2 + NADPH + H+
show the reaction diagram
-
-
-
?
10-formyltetrahydrofolate + NADP+ + H2O
tetrahydrofolate + CO2 + NADPH + H+
show the reaction diagram
-
-
-
?
10-formyltetrahydrofolate + NADP+ + H2O
tetrahydrofolate + CO2 + NADPH + H+
show the reaction diagram
-
-
-
?
10-formyltetrahydrofolate + NADP+ + H2O
tetrahydrofolate + CO2 + NADPH + H+
show the reaction diagram
-
-
-
ir
10-formyltetrahydrofolate + NADP+ + H2O
tetrahydrofolate + CO2 + NADPH + H+
show the reaction diagram
-
natural substrate
-
?
10-formyltetrahydrofolate + NADP+ + H2O
tetrahydrofolate + CO2 + NADPH + H+
show the reaction diagram
-
recycling of excess 10-formyltetrahydrofolate that is not needed for purine biosynthesis and restoration of the tetrahydrofolate pool, important for formate metabolism by clearing it as CO2 and thus protecting cells from formate intoxication
-
?
10-formyltetrahydrofolate + NADP+ + H2O
tetrahydrofolate + CO2 + NADPH + H+
show the reaction diagram
-
enzyme is an important factor in regulation of formate oxidation and is related with methanol poisoning
-
?
10-formyltetrahydrofolate + NADP+ + H2O
tetrahydrofolate + CO2 + NADPH + H+
show the reaction diagram
-
regulatory mechanism to control the in vivo folate pool size
-
?
10-formyltetrahydrofolate + NADP+ + H2O
tetrahydrofolate + CO2 + NADPH + H+
show the reaction diagram
-
disposal of excess one-carbon units, oxidation of one-carbon moieties is regulated by the ratio of formyltetrahydrofolate to tetrahydrofolate in liver, regulation of the proportion of folate present in the tetrahydrofolate form, presumably to make it available for other reactions of one-carbon metabolism
-
?
10-formyltetrahydrofolate + NADP+ + H2O
tetrahydrofolate + CO2 + NADPH + H+
show the reaction diagram
-
regulation of the ratio of 10-formyltetrahydrofolate to tetrahydrofolate in the cell in response to yet unknown aldehyde and thiol metabolites
-
?
10-formyltetrahydrofolate + NADP+ + H2O
tetrahydrofolate + CO2 + NADPH + H+
show the reaction diagram
-
a major liver enzyme, contributing to more than one metabolic pathway, regeneration of the tetrahydrofolate pool, not essential for viability
-
?
10-formyltetrahydrofolate + NADP+ + H2O
tetrahydrofolate + CO2 + NADPH + H+
show the reaction diagram
-
folate-dependent metabolism of formate to carbon dioxide
-
?
10-formyltetrahydrofolate + NADP+ + H2O
tetrahydrofolate + CO2 + NADPH + H+
show the reaction diagram
-
regulation of the ratio of 10-formyltetrahydrofolate to tetrahydrofolate and of the purine biosynthesis through control of the level of 10-formyltetrahydrofolate, down-regulation of FDH in tumors is one of the cellular mechanisms that enhance proliferation, FDH possesses tumor specific suppressor effects
-
?
10-formyltetrahydrofolate + NADP+ + H2O
tetrahydrofolate + CO2 + NADPH + H+
show the reaction diagram
-
major disposal route for excess one-carbon units produced in folate-mediated metabolism
-
?
10-formyltetrahydrofolate + NADP+ + H2O
tetrahydrofolate + CO2 + NADPH + H+
show the reaction diagram
-
folate-dependent pathway is the exclusive route of formate metabolism in primates, plays major role in disposition of formate generated from one-carbon moieties of environmental chemicals, drugs, and foods, importance in the toxicity of methanol
-
?
10-formyltetrahydrofolate + NADP+ + H2O
tetrahydrofolate + CO2 + NADPH + H+
show the reaction diagram
-
a major folate-binding protein of liver cytosol, 10-formyltetrahydrofolate polyglutamates are tightly bound in vivo
-
?
10-formyltetrahydropteroylhexaglutamate + NADP+ + H2O
tetrahydropteroylhexaglutamate + CO2 + NADPH
show the reaction diagram
-
-
-
?
10-formyltetrahydropteroylpentaglutamate + NADP+ + H2O
tetrahydropteroylpentaglutamate + CO2 + NADPH
show the reaction diagram
-
-
-
?
10-formyltetrahydropteroylpentaglutamate + NADP+ + H2O
tetrahydropteroylpentaglutamate + CO2 + NADPH
show the reaction diagram
-
natural substrate
-
?
10-formyltetrahydropteroylpentaglutamate + NADP+ + H2O
tetrahydropteroylpentaglutamate + CO2 + NADPH
show the reaction diagram
-
important site of binding of folylpolyglutamates in liver, regulation of the interconversion of 10-formyltetrahydropteroylpolyglutamate to tetrahydropteroylpolyglutamate and therefore of the high-energy formyl charge of the cell
-
ir
additional information
?
-
-
enzyme functions not as an aldehyde dehydrogenase in vivo, 10-formyltetrahydrofolate hydrolase activity is of no physiological significance, disulfiram may inhibit enzyme activity and probably perturb hepatic folate metabolism in vivo
-
-
-
additional information
?
-
-
FDH-expressing cells show accumulation of cells in G0-G1 phase and a sharp decrease of cells in S phase. Accumulation of the tumor suppressor protein p53 and its downstream target p21. FDH antiproliferative effects on A549 cells include both G1 cell cycle arrest and caspase-dependent apoptosis
-
-
-
additional information
?
-
-
activation of p53 tumor suppressor protein-dependent pathways is a general downstream mechanism in response to induction of enzyme expression in p53 functional cancer cells
-
-
-
COFACTOR
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
10-formyltetrahydrofolate
-
10-formyltetrahydrofolate
10-formyltetrahydrofolate
-
10-formyltetrahydrofolate
10-formyltetrahydrofolate
-
10-formyltetrahydrofolate; pentaglutamate form as coenzyme is very tightly bound to enzyme
10-formyltetrahydrofolate
-
10-formyltetrahydrofolate; 10-formyltetrahydrofolate is one of the most labile of the reduced coenzymes
10-formyltetrahydrofolate
-
10-formyltetrahydrofolate as coenzyme
10-formyltetrahydrofolate
-
10-formyltetrahydrofolate
5-formyltetrahydrofolate
-
covalent linkage of 5-formyltetrahydrofolate to enzyme, 2 mol bound per mol of enzyme monomer, it is a minor form of the folate coenzymes and arises from 10-formyltetrahydrofolate
folate
-
2 mol of folate bound per mol of enzyme monomer, consistent with the presence of two active sites
folate
-
10-formyl-5,8-dideazafolate and 5,8-dideazafolate
NAD+
-
less than 5% of the activity with NADP+
NADP+
-
specific for
NADP+
-
specific for
NADP+
-
NADP+-dependent; specific for
NADP+
-
binding of substrate, 10-formyltetrahydrofolate or propanal, influences enzyme affinity for NADP+; NADP+-dependent
NADP+
-
NADP+-dependent
NADP+
-
NADP+-dependent
tetrahydrofolate
-
-
tetrahydrofolate
-
very tight binding
tetrahydrofolate
-
as coenzyme
folate
-
10-formyl-5,8-dideazafolate and 5,8-dideazafolate
additional information
-
no effect: NADPH
-
INHIBITORS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
5,10-dideazatetrahydrofolate
-
0.4 mM, 98% inhibition, folate analog
5-formyltetrahydrofolate
-
covalent attachment completely inhibits
Chymotrypsin
-
cleavage between the two domains, inactivates 10-formyltetrahydrofolate dehydrogenase but not hydrolase and aldehyde dehydrogenase activity
-
hydroxylamine
-
0.1 M, strong inhibition
N-ethylmaleimide
-
1 mM or 10 mM, complete inhibition
p-chloromercuribenzoate
-
inhibition reversed by 2-mercaptoethanol
propanal
-
FDH activity decreases with increasing concentrations, competes with 10-formyltetrahydrofolate for NADP+-dependent oxidation
Subtilisin
-
cleavage between the two domains, inactivates 10-formyltetrahydrofolate dehydrogenase but not hydrolase and aldehyde dehydrogenase activity
-
tetrahydrofolate
-
strong product inhibition by both isomers
tetrahydrofolate
-
very strong product inhibition
tetrahydrofolate
-
competitive to 10-formyltetrahydrofolate and non-competitive to NADP+; very strong product inhibition
tetrahydrofolate
-
potent, competitive product inhibitor
tetrahydrofolate
-
-
tetrahydrofolate
-
potent, competitive product inhibitor
tetrahydropteroylhexaglutamate
-
1 mol per mol of tetrameric protein, potent product inhibitor: 0.0003 mM, 90% inhibition
Tetrahydropteroylpentaglutamate
-
strong product inhibition
tetrahydropteroylpolyglutamate
-
inhibition increases with increasing length of polyglutamyl chain
tetrahydropteroylpolyglutamate
-
potent product inhibitor
tetrahydropteroylpolyglutamate
-
inhibition increases with increasing length of polyglutamyl chain; potent product inhibitor
Trypsin
-
tryptic digestion inactivates 10-formyltetrahydrofolate dehydrogenase but not hydrolase activity
-
Trypsin
-
20 min, 70% inhibition, rapid but incomplete loss of dehydrogenase activity; tryptic digestion inactivates 10-formyltetrahydrofolate dehydrogenase but not hydrolase activity
-
Trypsin
-
cleavage between the two domains, inactivates 10-formyltetrahydrofolate dehydrogenase but not hydrolase and aldehyde dehydrogenase activity
-
iodoacetamide
-
inhibition reversed by 2-mercaptoethanol
additional information
-
-
-
additional information
-
not inhibited by (+)-10-formyltetrahydrofolate, 5-formyltetrahydrofolate, 5-methyltetrahydrofolate, folate, aminopterin, tetrahydroaminopterin
-
additional information
-
not inhibited by NADPH
-
additional information
-
not inhibited by the folate analog N-[4-[[3-(2,4-diamino-1,6-dihydro-6-oxo-5-pyrimidinyl)propyl]amino]-benzoyl]-L-glutamate
-
additional information
-
recombinant FDH is not inhibited by sodium azide
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
2-mercaptoethanol
-
5 to 15 mM: 1.7fold increase in activity, higher concentrations have no further effect, it may reduce oxidized Cys-707 or another important sulfhydryl group
2-mercaptoethanol
-
dehydrogenase and hydrolase activities are dependent on the presence of high concentrations of 2-mercaptoethanol to prevent the oxidative degradation of the substrate 10-formyltetrahydrofolate
2-mercaptoethanol
-
optimal dehydrogenase activity requires 15 mM or higher concentrations
4'-phosphopantetheinyl transferase
-
4'-phosphopantetheinyl transferase activates dehydrogenase catalysis of ALDH1L2 by modifying Ser375
-
NADPH
-
activates at concentrations and in ratio with NADP+ consistent with those in rat liver in vivo, activation is associated with higher Ki-value for tetrahydrofolate
serine hydroxymethyltransferase
-
addition of SHMT and of its substrate L-serine increases the initial reaction rate by 1.8fold with 10-formyltetrahydropteroylpentaglutamate as substrate, SHMT increases the release of product
-
C1-tetrahydrofolate synthase
-
10-formyltetrahydrofolate synthetase activity of trifunctional enzyme causes together with its substrates MgATP, formate, and tetrahydrofolate an 3fold increase of initial velocity
-
additional information
-
not activated by methionine or ethionine
-
KM VALUE [mM]
KM VALUE [mM] Maximum
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.0032
-
10-formyl-5,8-dideazafolate
-
-
0.0044
-
10-formyltetrahydrofolate
-
racemic, fluorimetric assay
0.0045
-
10-formyltetrahydrofolate
-
at pH 7
0.0055
-
10-formyltetrahydrofolate
-
-
0.007
-
10-formyltetrahydrofolate
-
-
0.0075
-
10-formyltetrahydrofolate
-
racemic, spectrophotometric assay
0.0082
-
10-formyltetrahydrofolate
-
(-)-isomer
0.0114
-
10-formyltetrahydrofolate
-
at pH 7.0 and 30C
0.0127
-
10-formyltetrahydrofolate
E3NZ06
30C, pH not specified in the publication, recombinant N-terminal domain
0.013
-
10-formyltetrahydrofolate
-
-
0.0156
-
10-formyltetrahydrofolate
E3NZ06
30C, pH not specified in the publication, full-length recombinant enzyme
0.017
-
10-formyltetrahydrofolate
-
racemic
0.02
-
10-formyltetrahydrofolate
-
-
0.0004
-
NADP+
-
spectrophotometric assay
0.0006
-
NADP+
-
fluorimetric assay
0.00086
-
NADP+
-
with 10-formyl-5,8-dideazafolate as substrate
0.00088
-
NADP+
-
with 10-formyltetrahydrofolate as substrate
0.00092
-
NADP+
-
at pH 7
0.0035
-
NADP+
-
-
0.05
-
10-formyltetrahydrofolate
-
-
additional information
-
additional information
-
-
-
TURNOVER NUMBER [1/s]
TURNOVER NUMBER MAXIMUM[1/s]
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.967
-
10-formyltetrahydrofolate
-
-
1
-
10-formyltetrahydrofolate
-
-
97
-
10-formyltetrahydrofolate
E3NZ06
30C, pH not specified in the publication, full-length recombinant enzyme
0.867
-
10-formyltetrahydropteroylpentaglutamate
-
with excess substrate, reaction cycle in combination with C1-tetrahydrofolate synthase, lower value than for dehydrogenase alone
0.9
-
10-formyltetrahydropteroylpentaglutamate
-
at 30C
Ki VALUE [mM]
Ki VALUE [mM] Maximum
INHIBITOR
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.048
-
5,10-dideazatetrahydrofolate
-
-
0.001
-
tetrahydrofolate
-
(-)-isomer
0.001
-
tetrahydrofolate
-
-
0.007
-
tetrahydrofolate
-
-
0.007
-
tetrahydrofolate
-
(-)-isomer
0.01
-
tetrahydrofolate
-
(+)-isomer
SPECIFIC ACTIVITY [µmol/min/mg]
SPECIFIC ACTIVITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
0.00278
-
-
liver samples enriched for cytosolic proteins, heterozygous mice with deletion mutation in the FDH structural gene
0.00478
-
-
liver samples enriched for cytosolic proteins, normal mice
0.094
-
-
recombinant FDH, 10-formyltetrahydrofolate as substrate
0.144
-
-
with 10-formyl-5,8-dideazafolate as substrate
0.26
-
-
with 10-formyltetrahydrofolate as substrate
0.305
-
-
-
0.51
-
-
-
0.64
-
-
-
0.7
0.8
-
at 25C
0.98
-
-
-
1.04
-
E3NZ06
30C, pH not specified in the publication, recombinant enzyme expressed in Pichia pastoris
additional information
-
-
-
additional information
-
-
-
additional information
-
-
no detectable activity in homozygous mice with deletion mutation in the FDH structural gene
pH OPTIMUM
pH MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
7.5
8.5
-
in Tris buffer 30% faster reaction than in phosphate buffer
7.8
-
-
broad pH-optimum centers at pH 7.8
8
-
-
broad pH-maximum at pH 8.0
pH RANGE
pH RANGE MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
6.5
8.5
-
more than 60% of maximal activity at pH 6.5 and 8.5
TEMPERATURE OPTIMUM
TEMPERATURE OPTIMUM MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
22
-
-
assay at
25
-
-
assay at
30
-
-
assay at
30
-
-
assay at
30
-
-
assay at
30
-
-
assay at
30
-
-
assay at
30
-
-
assay at
37
-
-
maximal catalytic capacity at
additional information
-
-
assay at room temperature
additional information
-
-
enzyme activity at 37C is twice that at 25C
pI VALUE
pI VALUE MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
5.6
-
Q5HZB2
predicted
7
-
Q5HZB2
two-dimensional gel electrophoresis
SOURCE TISSUE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
SOURCE
-
significantly decreased levels of FDH and its mRNA in 15 tested tumors compared with normal tissues, strong down-regulation of FDH on both the mRNA and protein level in tumors
Manually annotated by BRENDA team
-
inducible expression of 10-formyltetrahydrofolate dehydrogenase
Manually annotated by BRENDA team
-
moderate FDH mRNA level
Manually annotated by BRENDA team
O75891, Q3SY69
most highly expressed in pancreas, heart and brain
Manually annotated by BRENDA team
-
less activity
Manually annotated by BRENDA team
-
moderate FDH mRNA level
Manually annotated by BRENDA team
O75891, Q3SY69
most highly expressed in pancreas, heart and brain
Manually annotated by BRENDA team
-
transformed embryonic kidney cell line HEK-293A
Manually annotated by BRENDA team
-
mainly expressed in
Manually annotated by BRENDA team
-
high FDH mRNA level, specialized organ of folate metabolism
Manually annotated by BRENDA team
O75891, Q3SY69
; most highly expressed in pancreas, liver and kidney
Manually annotated by BRENDA team
-
activity in human liver is 26% of that in rat liver, reduced amount of enzyme in human liver
Manually annotated by BRENDA team
-
mainly expressed in fetal liver
Manually annotated by BRENDA team
-
very high concentrations, two livers, 120 g, contain about 360 mg enzyme
Manually annotated by BRENDA team
-
high FDH mRNA level; specialized organ of folate metabolism
Manually annotated by BRENDA team
-
high FDH mRNA level
Manually annotated by BRENDA team
-
feeding of ethanol decreases hepatic enzyme activity, decrease occurs irrespective of folate status
Manually annotated by BRENDA team
O75891, Q3SY69
most highly expressed in pancreas, liver and kidney
Manually annotated by BRENDA team
-
mainly expressed in skeletal muscle
Manually annotated by BRENDA team
-
moderate FDH mRNA level in skeletal muscle
Manually annotated by BRENDA team
-
moderate FDH mRNA level
Manually annotated by BRENDA team
-
high FDH mRNA level
Manually annotated by BRENDA team
O75891, Q3SY69
most highly expressed in pancreas, heart and brain; most highly expressed in pancreas, liver and kidney
Manually annotated by BRENDA team
-
moderate FDH mRNA level
Manually annotated by BRENDA team
-
much lower levels than in liver, preferentially localized in Mller cells, FDH levels in human retina are higher than in rat retina, folate levels in human retina are 14% of those in rat retina
Manually annotated by BRENDA team
-
less activity
Manually annotated by BRENDA team
-
moderate FDH mRNA level
Manually annotated by BRENDA team
-
moderate FDH mRNA level
Manually annotated by BRENDA team
-
moderate FDH mRNA level
Manually annotated by BRENDA team
additional information
-
FDH expression is highly tissue specific, very low or nondetectable levels of FDH mRNA in placenta, spleen, colon, small intestine, and leukocytes
Manually annotated by BRENDA team
additional information
O75891, Q3SY69
cytosolic FDH mRNa is not detectable in cancer cells; In contrast to the cytosolic enzyme, mtFDH mRNA and protein are clearly present in cancer cell lines
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
-
primarily or exclusively localized in
Manually annotated by BRENDA team
-
comparable amounts of cytosolic and mitochondrial FDH in retinal tissues
Manually annotated by BRENDA team
-
small amount, 0.4% of total liver dehydrogenase activity
Manually annotated by BRENDA team
-
comparable amounts of cytosolic and mitochondrial FDH in retinal tissues
Manually annotated by BRENDA team
additional information
-
not detected in nucleus, lysosomes or peroxisomes
-
Manually annotated by BRENDA team
MOLECULAR WEIGHT
MOLECULAR WEIGHT MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
58000
-
-
C-terminal domain, gel filtration
90000
-
-
SDS-PAGE
100000
-
-
full-length enzyme, gel filtration
320000
-
-
gel filtration
390000
-
-
gel filtration
393200
-
-
C707A mutant FDH, molecular size detector employing laser-light scattering methodology
398800
-
-
wild-type FDH, molecular size detector employing laser-light scattering methodology
400000
-
E3NZ06
gel fitlration
413000
-
-
gel filtration, sedimentation analysis
440000
-
-
gel filtration
450000
-
-
nondenaturing PAGE
SUBUNITS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
?
-
x * 94000, SDS-PAGE
?
-
x * 96000, SDS-PAGE
?
-
x * 99015, SDS-PAGE
?
-
x * 99000, SDS-PAGE
?
-
x * 98700, protein with 902 amino acids, calculated from cDNA
?
-
x * 96000, MSN13/94, identified as forms of FDH, two-dimensional electrophoresis
?
Q5HZB2
x * 100000, two-dimensional gel electrophoresis; x * 99700, predicted
?
O75891, Q3SY69
x * 130000, green fluorescent protein fusion construct, SDS-PAGE
homotetramer
-
4 * 92500, SDS-PAGE
homotetramer
-
-
homotetramer
-
4 * 91000, three minor bands of 63000, 58000 and 39000, SDS-PAGE
homotetramer
-
4 * 108000, SDS-PAGE
homotetramer
-
4 * 99000, SDS-PAGE
homotetramer
-
monomer with 902 amino acid residues
homotetramer
-
4 * 99000, SDS-PAGE; monomer with 902 amino acid residues
homotetramer
-
4 * 106000, SDS-PAGE
homotetramer
-
4 * 99000, wild-type FDH and C707A mutant
homotetramer
-
4 * 14500, C-terminal domain, SDS-PAGE
tetramer
E3NZ06
4 * 100000, calculated
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
phospholipoprotein
-
the broad specificity human 4-phosphopantetheinyl transferase phosphopantetheinylates apo-FDH to holoenzyme and thus activates FDH catalysis. Silencing 4-phosphopantetheinyl transferase by small interfering RNA in A-549 cells prevents FDH modification
additional information
-
protein with conserved potential N-glycosylation sites, protein kinase phosphorylation sites, and N-myristoylation sites, post-translational modification may be important for the function
additional information
-
S375 is the putative site of enzyme phosphopantetheinylation
proteolytic modification
O75891, Q3SY69
sequence contains a 22 amino acid N-terminal mitochondrial translocation signal
additional information
-
FDH requires posttranslational modification to become a functional enzyme (4'-phosphopantetheine prosthetic group)
Crystallization/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
C-terminal domain of FDH and its complexes with oxidized and reduced forms of NADP+ are crystallized using the hanging drop vapour diffusion method with 1.4-1.5 M ammonium sulfate and 0.1 M Tris-HCl, pH 7.0-7.5
-
crystal structure of the hydrolase domain of FDH, solved to 2.3 A resolution
-
GENERAL STABILITY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
in general activity is labile
-
OXIDATION STABILITY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
prone to oxidative inactivation, but may be partially reactivated by incubation with 100 mM 2-mercaptoethanol or 100 mM dithiothreitol
-
392342
STORAGE STABILITY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
-20C, 20% glycerol, several months, stable
-
-20C, 20% glycerol, over 12 months, no loss of activity
-
-20C, stable for several months
-
-70C, 0.05 M phosphate buffer, pH 7.2, 50%-saturated (NH4)2SO4, 20% glycerol, 1 mM EDTA, 0.1 mM dithioerythritol, 0.01 mM phenylmethanesulfonyl fluoride, several months, stable
-
4C, stable for 2 weeks
-
-15C, presence of 0.01 mM 2-mercaptoethanol, several weeks, stable
-
-20C, dialyzed against 0.01 M potassium phosphate buffer, pH 7.3, 40% glycerol, 0.1 M KCl, several weeks, stable
-
Purification/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
recombinant protein
E3NZ06
free of 10-formyltetrahydrofolate hydrolase activity
-
partial purification of MSN13/94, identified as forms of 10-formyltetrahydrofolate dehydrogenase
-
250fold purification
-
5-fTHFSepharose column chromatography, Sephacryl S-300 gel filtration, and MonoQ column chromatography
-
co-purification with carbamoyl-phosphate synthetase 1 and betaine homocysteine S-methyltransferase using Kunitz-type soybean trypsin inhibitor-coupled Sepharose CL-4B column chromatography, Sephacryl S-200 gel filtration, and Superdex 200 gel filtration; Kunitz-type soybean trypsin inhibitor-coupled Sepharose CL-4B column chromatography
-
free of 10-formyltetrahydrofolate hydrolase activity
-
intermediate domain and its mutants
-
Ni-NTA column chromatography
-
purification of a C707A mutant of FDH; purification of recombinant liver FDH
-
purification of N-terminal domain mutants and of a D124A mutant of FDH
-
purification of N-terminal domain mutants and of a H106K mutant of FDH
-
purification of recombinant 310 amino acid residue N-terminal domain
-
purification of recombinant liver FDH
-
separated from 10-formyltetrahydrofolate hydrolase, dehydrogenase and hydrolase are closely related and separately compartmentalized enzymes
-
200fold partial purification
-
Cloned/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
expression in Escherichia coli and Pichia pastoris
E3NZ06
; transfection of COS-7 and A-549 cells, and expression with green fluorescent protein fusion construct
O75891, Q3SY69
cloning and sequencing of the cDNA encoding FDH from fetal liver
-
cloning of the cDNA encoding FDH, cells from several tumor cell lines are transfected with FDH cDNA cloned into pcDNA 3.1+ vector using LipofectAMINE, expression of FDH inhibits the proliferation of the cell lines as a result of its enzymatic activity
-
expressed in Escherichia coli BL21(DE3) Codon Plus cells
-
expression in Escherichia coli
-
clone expressed in insect cells has both dehydrogenase and hydrolase activity and exhibits almost identical kinetic parameters to the native rat liver enzyme; FDH is cloned
-
cloning of the cDNA encoding FDH
-
cloning of the cDNA encoding FDH; expression of FDH cDNA, subcloned in the pVL 1393 baculovirus vector, in Sf9 insect cells, using the MaxBac expression system
-
expressed in Escherichia coli
-
expressed in Escherichia coli and Sf9 insect cells
-
expression of D124A mutant of FDH and N-terminal domain mutants in Sf9 insect cells, using a baculovirus expression system
-
expression of FDH and its N-terminal and C-terminal domains in insect cells, using a baculovirus expression system, expression of FDH and of its 310 amino acid residue N-terminal domain in Escherichia coli BL21 using the pRSET vector, full-length enzyme expressed in Escherichia coli is nonsoluble, because of the large size of its monomer and uncorrect folding in prokaryotic cells
-
expression of FDH cDNA, subcloned in the pVL 1393 baculovirus vector, in Sf9 insect cells, using the MaxBac expression system
-
expression of FDH in insect cells using the pVL 1393 baculovirus expression vector
-
expression of H106K mutant of FDH in insect cells SF9, using a baculovirus expression system, and of N-terminal domain mutants in Escherichia coli BL 21
-
FDH is cloned
-
ENGINEERING
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
C707A
-
catalytically inactive mutant
S374A
-
the mutant is activated by 4'-phosphopantetheinyl transferase
S374A/S375A
-
the mutant is not activated by 4'-phosphopantetheinyl transferase
C152A
-
95% of the activity with wild-type enzyme
C17A
-
94% of the activity with wild-type enzyme
C191A
-
96% of the activity with wild-type enzyme
C238A
-
102% of the activity with wild-type enzyme
C707A
-
mutant with a complete loss of NADP+-dependent 10-formyltetrahydrofolate dehydrogenase activity, but no influence on hydrolase activity
C707A
-
mutant with a complete loss of dehydrogenase activity of 10-formyltetrahydrofolate and propanal, but hydrolase activity and binding of NADP+ is unchanged
C86A
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110% of the activity with wild-type enzyme
D142A
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mutant with a complete loss of 10-formyltetrahydrofolate dehydrogenase and hydrolase activity, aldehyde dehydrogenase activity is similar to wild-type FDH
D399A
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90% of the dehydrogenase activity of the wild-type enzyme
E398A
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90% of the dehydrogenase activity of the wild-type enzyme
F384_V405del
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no dehydrogenase activity
G397A
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as active as wild-type enzyme
H106A
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insoluble recombinant protein
H106K
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mutant with a complete loss of 10-formyltetrahydrofolate dehydrogenase and hydrolase activity, aldehyde dehydrogenase activity is similar to wild-type FDH
K394A
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75% of the dehydrogenase activity of the wild-type enzyme
K394A/L395A/R396A/G397A/E398A/D399A
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no dehydrogenase activity
K394_D399del
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no dehydrogenase activity
L395A
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80% of the dehydrogenase activity of the wild-type enzyme
R396A
-
as active as wild-type enzyme
S354A
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no dehydrogenase activity
S375A
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the mutant is not activated by 4'-phosphopantetheinyl transferase
additional information
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deletion mutation in the 10-formyltetrahydrofolate structural gene in homozygous mice with absence of FDH mRNA and enzyme activity, total folate pool is decreased and the level of tetrahydrofolate is markedly depleted, pairs of homozygotes have a dramatically decreased reproductive efficiency, may be attributable to fetal lethality
APPLICATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
medicine
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formic acidemia: toxicity of methanol in humans is correlated with formate accumulation as a result of low rates of formate oxidation, which is in vivo dependent on enzyme activity and on hepatic tetrahydrofolate levels
medicine
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formic acidemia: toxicity of methanol in humans is correlated with formate accumulation as a result of low rates of formate oxidation, which is in vivo dependent on enzyme activity and on hepatic tetrahydrofolate levels; methanol-induced toxicity in Mller cells of the retina, role of 10-FDH in formate intoxination both as a protectant and as a toxicity-provoking element
medicine
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enzyme-induced suppressor effects are strictly dependent on p53 tumor suppressor protein in A549 cells. Enzyme elevation results in p53 phosphorylation at S6 and S20 in the p53 transactivation domain, and S392 in the C-terminal domain, but only S6 is strictly required to mediate enzyme effects
medicine
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feeding of ethanol decreases hepatic enzyme activity, decrease occurs irrespective of folate status