Information on EC 4.2.1.2 - fumarate hydratase

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The expected taxonomic range for this enzyme is: Brevibacterium

EC NUMBER
COMMENTARY
4.2.1.2
-
RECOMMENDED NAME
GeneOntology No.
fumarate hydratase
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
(S)-malate = fumarate + H2O
show the reaction diagram
-
-
-
-
(S)-malate = fumarate + H2O
show the reaction diagram
mechanism
-
(S)-malate = fumarate + H2O
show the reaction diagram
the enzyme follows a fully reversible 11-tate multistep catalytic mechanism, detailed overview
-
REACTION TYPE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
C-O bond cleavage by elimination of water
-
-
C-O bond formation
-
-
elimination
-
-
-
-
PATHWAY
KEGG Link
MetaCyc Link
anaerobic energy metabolism (invertebrates, mitochondrial)
-
Biosynthesis of secondary metabolites
-
Carbon fixation pathways in prokaryotes
-
Citrate cycle (TCA cycle)
-
incomplete reductive TCA cycle
-
Metabolic pathways
-
methylaspartate cycle
-
Microbial metabolism in diverse environments
-
mixed acid fermentation
-
pyruvate fermentation to propionate I
-
Pyruvate metabolism
-
reductive TCA cycle I
-
reductive TCA cycle II
-
respiration (anaerobic)
-
superpathway of glyoxylate cycle and fatty acid degradation
-
TCA cycle I (prokaryotic)
-
TCA cycle II (plants and fungi)
-
TCA cycle III (helicobacter)
-
TCA cycle IV (2-oxoglutarate decarboxylase)
-
TCA cycle V (2-oxoglutarate:ferredoxin oxidoreductase)
-
TCA cycle VI (obligate autotrophs)
-
TCA cycle VII (acetate-producers)
-
TCA cycle VIII (metazoan)
-
SYSTEMATIC NAME
IUBMB Comments
(S)-malate hydro-lyase (fumarate-forming)
-
SYNONYMS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
class II fumarase
P39461
-
class II fumarase
Sulfolobus solfataricus MT-4
P39461
-
-
class II fumarase
-
-
FUM C
-
FUM isozyme capable of hydrating fumarate without the aid of Fe-S clusters
FUM C
Pseudomonas fluorescens 13525
-
FUM isozyme capable of hydrating fumarate without the aid of Fe-S clusters
-
fumarase
-
-
-
-
fumarase
P93033, Q9FI53
-
fumarase
-
-
-
fumarase
-
-
fumarase
P55250
-
fumarase
-
-
fumarase
P39461
-
fumarase
Sulfolobus solfataricus MT-4
P39461
-
-
fumarase
-
-
fumarase C
-
-
fumarase C
Pseudomonas fluorescens 13525
-
-
-
fumarase C
A5Y6J1
-
fumarate hydratase
-
-
FumC
Escherichia coli FumC
-
-
-
FUMR
P55250
-
hydratase, fumarate
-
-
-
-
L-malate hydro-lyase
-
-
-
-
CAS REGISTRY NUMBER
COMMENTARY
9032-88-6
-
ORGANISM
COMMENTARY
LITERATURE
SEQUENCE CODE
SEQUENCE DB
SOURCE
synthrophic propionate-oxidizing bacterium strain MPOB
-
-
Manually annotated by BRENDA team
isolate RMIT 32A; strain ATCC 33559
-
-
Manually annotated by BRENDA team
subsp. fetus ATCC 33246 and subsp. venerealis strain ATCC 19438
-
-
Manually annotated by BRENDA team
2 types of enzyme: Fe-independent FUMC and Fe-dependent FUMA; W
-
-
Manually annotated by BRENDA team
3 fumarases FUMA, FUMB, and FUMC
-
-
Manually annotated by BRENDA team
contains three biochemically distinct fumarases: FumA, FumB and FumC
-
-
Manually annotated by BRENDA team
fumarase A
-
-
Manually annotated by BRENDA team
fumarase C
-
-
Manually annotated by BRENDA team
one Fe-S-dependent enzyme form and one Fe-S-independent enzyme form
-
-
Manually annotated by BRENDA team
Escherichia coli FumC
FumC
-
-
Manually annotated by BRENDA team
var. bacillaris
-
-
Manually annotated by BRENDA team
Geobacillus stearothermophilus NU-10
NU-10
-
-
Manually annotated by BRENDA team
gene HP1325
-
-
Manually annotated by BRENDA team
-
SwissProt
Manually annotated by BRENDA team
homozygous carriers of the mutation Q376P suffer from severe encephalopthy and die at a young age
-
-
Manually annotated by BRENDA team
Mesembryanthemum crystallinum L.
L.
-
-
Manually annotated by BRENDA team
possesses at least two and possibly three fumarases
-
-
Manually annotated by BRENDA team
strain 13525
-
-
Manually annotated by BRENDA team
Pseudomonas fluorescens 13525
strain 13525
-
-
Manually annotated by BRENDA team
gene fumR
UniProt
Manually annotated by BRENDA team
strains BY4741 and BY4743
-
-
Manually annotated by BRENDA team
strain MT-4 (ATCC 49155)
UniProt
Manually annotated by BRENDA team
Sulfolobus solfataricus DSM 1616
-
-
-
Manually annotated by BRENDA team
Sulfolobus solfataricus MT-4
strain MT-4 (ATCC 49155)
UniProt
Manually annotated by BRENDA team
several isoenzymes
-
-
Manually annotated by BRENDA team
X-1
-
-
Manually annotated by BRENDA team
Thermus sp. X-1
X-1
-
-
Manually annotated by BRENDA team
AS-15-1, class II fumarase
-
-
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
malfunction
Q9FI53
fumarase activity in extracts of leaves of fum2 mutants is reduced by approximately 85% relative to the wild-type. In the fum2-1 mutant, fumarate is present at a 10fold lower level and malate at a 2fold higher level than in the wild-type. Fum2-1 plants accumulate twice as much starch as the wild-type; isolation of homozygous fum1 knock-out plants from self-fertilized heterozygotes is failing
malfunction
-
in the absence of cytosolic fumarate hydratase, the cellular response to DNA damage is impaired
malfunction
-
increased sensitivity (10-100fold) of the FUM1 mutant strain to ionizing radiation, to the presence of hydroxyurea and to double-strand breaks when compared to the wild-type. Cytosolic absence of fumarase in yeast with a DELTAfum1 chromosomal deletion can be complemented by human fumarase. Fumaric acid (25 mM) complements the phenotype of fumarase cytosolic absence. FUM1 mutant strain sensitivity to double-strand breaks can be complemented by catalytically active pDELTAMTS-FUM1 but not by the corresponding H153R mutant
metabolism
-
fumarase catalyzes the reversible hydration of fumarate to L-malate and is a key enzyme in the tricarboxylic acid cycle and in amino acid metabolism
physiological function
-
fumarase in permeabilized non-growing cells used as biocatalysts for continuous production of L-malic acid
physiological function
-
purified fumarase used as biocatalysts for continuous production of L-malic acid
physiological function
-
presence of lysine at amino acid position 481 in Dahl salt-sensitive rats and glutamic acid in Brown Norway and SS-13BN rats. The variation K481E likely contributes to the much higher specific activity of fumarase in SS-13BN rats. Total fumarase activity is significantly lower in the kidneys of Dahl salt-sensitive rats compared with SS-13BN rats, despite an apparent compensatory increase in fumarase abundance in Dahl salt-sensitive rats
physiological function
-
metabolites of the glyoxylate shunt act as nanosensors for fumarase subcellular targeting and distribution. Glyoxylate shunt deletion mutants exhibit an altered fumarase dual distribution. Expression levels of Cit2 affect dual targeting of fumarase. Amount of cytosolic fumarase is drastically reduced in the DELTAcit2 strain, when compared with the wild-type strain. Proportion of fumarase activity is very low in the cytosolic versus mitochondrial fractions obtained from DELTAcit2 and wild-type plus pCit2 strains when compared with the wild-type or DELTAcit2 plus pCit2 strains, in which the fumarase activity is divided equally between the corresponding subcellular fractions
physiological function
Q9FI53
FUM1 is an essential enzyme, consistent with its role in the tricarboxylic acid cycle; FUM2 accounts for much more activity than FUM1 in leaves. FUM2 is not required for seed germination and seedling growth. FUM2 is required for fumarate accumulation from malate in leaves. Accumulation of fumarate catalysed by FUM2 is required for effective assimilation of nitrogen and growth on high nitrogen
physiological function
-
fumarate hydratase and fumaric acid are critical elements of the DNA damage response, which underlies the tumor suppressor role of fumarate hydratase and which is most probably independent of hypoxia-inducible factor. Cytoplasmic version of fumarate hydratase has a role in repairing DNA double-strand breaks in the nucleus. This role involves the movement of fumarate hydratase from the cytoplasm into the nucleus and depends on its enzymatic activity. When fumarate hydratase is absent from cells, its function in DNA repair can be substituted by high concentrations of one of the enzyme's products, fumaric acid. Fumarate hydratase deficiency leads to cancer because there is not enough fumaric acid in the nucleus to stimulate repair of DNA double-strand breaks. Can complement the cytosolic absence of fumarase in yeast with a DELTAfum1 chromosomal deletion
physiological function
-
cytosolic fumarase plays a role in the cellular response to double-strand breaks. Fumarase enzymatic activity is required for its DNA damage protective function. Fumarase activity is also required for the extra-mitochondrial function of fumarase
physiological function
P55250, -
fumarase catalyzes the reversible hydration of fumarate to L-malate in Rhizopus oryzae
SUBSTRATE
PRODUCT                      
REACTION DIAGRAM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
(S)-malate
fumarate + H2O
show the reaction diagram
-
-
-
r
(S)-malate
fumarate + H2O
show the reaction diagram
-
-
-
-
-
(S)-malate
fumarate + H2O
show the reaction diagram
-
-
-
-
-
(S)-malate
fumarate + H2O
show the reaction diagram
-
-
-
r
(S)-malate
fumarate + H2O
show the reaction diagram
-
-
-
r
(S)-malate
fumarate + H2O
show the reaction diagram
-
-
-
-
?
(S)-malate
fumarate + H2O
show the reaction diagram
-
-
-
-
r
(S)-malate
fumarate + H2O
show the reaction diagram
-
-
-
-
(S)-malate
fumarate + H2O
show the reaction diagram
-
-
-
-
-
(S)-malate
fumarate + H2O
show the reaction diagram
-
-
-
-
r
(S)-malate
fumarate + H2O
show the reaction diagram
-
-
-
r
(S)-malate
fumarate + H2O
show the reaction diagram
-
-
-
-
r
(S)-malate
fumarate + H2O
show the reaction diagram
-
-
-
-
-
(S)-malate
fumarate + H2O
show the reaction diagram
-
-
-
-
?
(S)-malate
fumarate + H2O
show the reaction diagram
-
-
-
r
(S)-malate
fumarate + H2O
show the reaction diagram
-
-
-
r
(S)-malate
fumarate + H2O
show the reaction diagram
-
-
-
r
(S)-malate
fumarate + H2O
show the reaction diagram
-
-
-
-
?
(S)-malate
fumarate + H2O
show the reaction diagram
-
-
-
r
(S)-malate
fumarate + H2O
show the reaction diagram
-
-
-
-
r
(S)-malate
fumarate + H2O
show the reaction diagram
-
-
-
r
(S)-malate
fumarate + H2O
show the reaction diagram
-
-
-
-
?
(S)-malate
fumarate + H2O
show the reaction diagram
-
-
-
-
r
(S)-malate
fumarate + H2O
show the reaction diagram
-, Q8NRN8
-
-
-
r
(S)-malate
fumarate + H2O
show the reaction diagram
Q9FI53
-
-
-
?
(S)-malate
fumarate + H2O
show the reaction diagram
P55250, -
-
-
-
r
(S)-malate
fumarate + H2O
show the reaction diagram
-
-
wild-type enzyme is rate-limited in the recycling of free enzyme isoforms that follows product release
?
(S)-malate
fumarate + H2O
show the reaction diagram
Thermus sp. X-1
-
-
-
-
?
(S)-malate
fumarate + H2O
show the reaction diagram
Sulfolobus solfataricus DSM 1616
-
-
-
r
(S)-malate
fumarate + H2O
show the reaction diagram
Escherichia coli FumC
-
-
wild-type enzyme is rate-limited in the recycling of free enzyme isoforms that follows product release
?
(S)-malate
fumarate + H2O
show the reaction diagram
Geobacillus stearothermophilus NU-10
-
-
-
-
?
(S)-malate
fumarate + H2O
show the reaction diagram
-
-
-
-
r
2(S)-3(S)-tartrate
oxaloacetate
show the reaction diagram
-
-
-
-
acetylene dicarboxylate + H2O
oxaloacetate
show the reaction diagram
-
-
-
?
acetylene dicarboxylate + H2O
oxaloacetate
show the reaction diagram
-
-
-
?
alpha-fluorofumarate + H2O
oxaloacetate + ?
show the reaction diagram
-
-
-
?
alpha-fluorofumarate + H2O
oxaloacetate + ?
show the reaction diagram
-
-
-
-
?
bromofumarate + H2O
?
show the reaction diagram
-
-
-
-
?
chlorofumarate + H2O
?
show the reaction diagram
-
-
-
-
?
Fumarate + H2O
L-Malate
show the reaction diagram
-
-
-
-
Fumarate + H2O
L-Malate
show the reaction diagram
-
-
-
?
Fumarate + H2O
L-Malate
show the reaction diagram
-
-
-
r
Fumarate + H2O
L-Malate
show the reaction diagram
-
-
-
r
Fumarate + H2O
L-Malate
show the reaction diagram
P05042
-
-
r
Fumarate + H2O
L-Malate
show the reaction diagram
-
-
-
-
?
Fumarate + H2O
L-Malate
show the reaction diagram
-
-
-
r
Fumarate + H2O
L-Malate
show the reaction diagram
-
-
-
r
Fumarate + H2O
L-Malate
show the reaction diagram
-
-
-
-
?
Fumarate + H2O
L-Malate
show the reaction diagram
-
-
-
r
Fumarate + H2O
L-Malate
show the reaction diagram
-
-
-
r
Fumarate + H2O
L-Malate
show the reaction diagram
-
-
-
-
?
Fumarate + H2O
L-Malate
show the reaction diagram
-
-
-
r
Fumarate + H2O
L-Malate
show the reaction diagram
-
-
-
r
Fumarate + H2O
L-Malate
show the reaction diagram
-
-
-
r
Fumarate + H2O
L-Malate
show the reaction diagram
-
-
-
r
Fumarate + H2O
L-Malate
show the reaction diagram
-
-
-
-
?
Fumarate + H2O
L-Malate
show the reaction diagram
-, Q7Z1D9
-
-
?
Fumarate + H2O
L-Malate
show the reaction diagram
-
-
-
-
?
Fumarate + H2O
L-Malate
show the reaction diagram
-
-
-
r
Fumarate + H2O
L-Malate
show the reaction diagram
-
-
-
-
?
Fumarate + H2O
L-Malate
show the reaction diagram
-
-
-
-
Fumarate + H2O
L-Malate
show the reaction diagram
-
-
-
-
?
Fumarate + H2O
L-Malate
show the reaction diagram
P39461, -
-
-
-
r
Fumarate + H2O
L-Malate
show the reaction diagram
-
constitutive enzyme
-
?
Fumarate + H2O
L-Malate
show the reaction diagram
P05042
enzyme of Krebs cycle
-
r
Fumarate + H2O
L-Malate
show the reaction diagram
-
enzyme of Krebs cycle
-
r
Fumarate + H2O
L-Malate
show the reaction diagram
-
Fum A and FumC activities are induced 4fold to 5fold when the cell growth rate is lowered from 1.2/h to 0.24/h at 1% and 21% O2. Twofold induction of FumA and FumC activities when acetate is utilized instead of glucose as the sole carbon source. Growth rate control of FumA and FumC activities is cAMP dependent. While FumB activity is maximal during anaerobic groth, FumA is the major enzyme under anaerobic cell growth, and the maximal activity is achieved when oxygen is elevated to 1-2%. Further increrase in oxygen level causes inactivation of FumA and FumB activities
-
?
Fumarate + H2O
L-Malate
show the reaction diagram
-
in CAM plants fumarase is much lower than in C3 plants. Under low light and prolonged salt treatment, an increase of fumarase activity is detected. This change is not observed at high light
-
?
Fumarate + H2O
L-Malate
show the reaction diagram
Sulfolobus solfataricus MT-4
P39461
-
-
-
r
Fumarate + H2O
L-Malate
show the reaction diagram
Mesembryanthemum crystallinum L.
-
in CAM plants fumarase is much lower than in C3 plants. Under low light and prolonged salt treatment, an increase of fumarase activity is detected. This change is not observed at high light
-
?
Fumarate + H2O
L-Malate
show the reaction diagram
Sulfolobus solfataricus DSM 1616
-
-
-
r
Fumarate + H2O
L-Malate
show the reaction diagram
Pseudomonas fluorescens 13525
-
-
-
-
?
fumaric acid + H2O
(S)-malic acid
show the reaction diagram
-
-
-
-
-
fumaric acid + H2O
L-malic acid
show the reaction diagram
-
-
-
-
-
iodofumarate + H2O
?
show the reaction diagram
-
-
-
-
?
L-tartrate
oxaloacetate + H2O
show the reaction diagram
-
-
-
?
L-threo-chloro-L-malate
chlorofumarate + H2O
show the reaction diagram
-
-
-
?
L-threo-hydroxyaspartate
?
show the reaction diagram
-
-
-
-
?
mesaconate + H2O
?
show the reaction diagram
-
-
-
-
?
additional information
?
-
-
enzyme of the tricarboxylic acid cycle
-
-
-
additional information
?
-
-
the iron-regulated tricarboxylic acid cycle enzyme fumarase C is essential for optimal alginate production by Pseudomonas aeruginosa
-
-
-
additional information
?
-
-
all missense mutations of fumarate hydratase associating with MCUL/hereditary leiomyomatosis and renal cell cancer show diminished fumarate hydratase enzymatic. It is suggested that the tumor suppressor role of fumarate hydratase may relate to its enzymatic function
-
-
-
additional information
?
-
-
stimulation of fumarase synthesis by changing medium components
-
-
-
additional information
?
-
-
germline mutations in fumarate hydratase gene at 1q43 predispose to hereditary leiomyomatosis and renal cell cancer (HLRCC) syndrome. In HLRCC, the most common clinical features are leiomyomas of the skin and uterus, and in a subset of the families, renal cell cancer (RCC) and uterine leiomyosarcoma (ULMS) occur frequently at young age. On the population level hereditary FH defects do play a role in pathogenesis of sporadic early onset ULMSs, albeit rarely
-
-
-
additional information
?
-
-
hereditary leiomyomatosis and renal cell cancer is a hereditary cancer syndrome predisposing individuals to the development of aggressive kidney cancer. These individuals harbour a germline mutation of fumarate hydratase
-
-
-
additional information
?
-
-
Leydig cell tumors are caused by fumarate hydratase mutations
-
-
-
additional information
?
-
-
tumorigenic effect of fumarate hydratase mutations involve more than one mechanism
-
-
-
additional information
?
-
-
fumarate hydratase is a key enzyme of the tricarboxylic cycle, hypoxia activation due to fumarate accumulation may be a tissue-specific response
-
-
-
additional information
?
-
Sulfolobus solfataricus, Sulfolobus solfataricus DSM 1616
-
no activity with D-malate, maleate, citramalate and citrate
-
-
-
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
(S)-malate
fumarate + H2O
show the reaction diagram
-
-
-
-
r
(S)-malate
fumarate + H2O
show the reaction diagram
-
-
-
-
r
(S)-malate
fumarate + H2O
show the reaction diagram
P55250, -
-
-
-
r
(S)-malate
fumarate + H2O
show the reaction diagram
-
-
-
-
r
Fumarate + H2O
L-Malate
show the reaction diagram
-
constitutive enzyme
-
?
Fumarate + H2O
L-Malate
show the reaction diagram
P05042
enzyme of Krebs cycle
-
r
Fumarate + H2O
L-Malate
show the reaction diagram
-
enzyme of Krebs cycle
-
r
Fumarate + H2O
L-Malate
show the reaction diagram
-
Fum A and FumC activities are induced 4fold to 5fold when the cell growth rate is lowered from 1.2/h to 0.24/h at 1% and 21% O2. Twofold induction of FumA and FumC activities when acetate is utilized instead of glucose as the sole carbon source. Growth rate control of FumA and FumC activities is cAMP dependent. While FumB activity is maximal during anaerobic groth, FumA is the major enzyme under anaerobic cell growth, and the maximal activity is achieved when oxygen is elevated to 1-2%. Further increrase in oxygen level causes inactivation of FumA and FumB activities
-
?
Fumarate + H2O
L-Malate
show the reaction diagram
Mesembryanthemum crystallinum, Mesembryanthemum crystallinum L.
-
in CAM plants fumarase is much lower than in C3 plants. Under low light and prolonged salt treatment, an increase of fumarase activity is detected. This change is not observed at high light
-
?
additional information
?
-
-
enzyme of the tricarboxylic acid cycle
-
-
-
additional information
?
-
-
the iron-regulated tricarboxylic acid cycle enzyme fumarase C is essential for optimal alginate production by Pseudomonas aeruginosa
-
-
-
additional information
?
-
-
all missense mutations of fumarate hydratase associating with MCUL/hereditary leiomyomatosis and renal cell cancer show diminished fumarate hydratase enzymatic. It is suggested that the tumor suppressor role of fumarate hydratase may relate to its enzymatic function
-
-
-
additional information
?
-
-
stimulation of fumarase synthesis by changing medium components
-
-
-
additional information
?
-
-
germline mutations in fumarate hydratase gene at 1q43 predispose to hereditary leiomyomatosis and renal cell cancer (HLRCC) syndrome. In HLRCC, the most common clinical features are leiomyomas of the skin and uterus, and in a subset of the families, renal cell cancer (RCC) and uterine leiomyosarcoma (ULMS) occur frequently at young age. On the population level hereditary FH defects do play a role in pathogenesis of sporadic early onset ULMSs, albeit rarely
-
-
-
additional information
?
-
-
hereditary leiomyomatosis and renal cell cancer is a hereditary cancer syndrome predisposing individuals to the development of aggressive kidney cancer. These individuals harbour a germline mutation of fumarate hydratase
-
-
-
additional information
?
-
-
Leydig cell tumors are caused by fumarate hydratase mutations
-
-
-
additional information
?
-
-
tumorigenic effect of fumarate hydratase mutations involve more than one mechanism
-
-
-
additional information
?
-
-
fumarate hydratase is a key enzyme of the tricarboxylic cycle, hypoxia activation due to fumarate accumulation may be a tissue-specific response
-
-
-
METALS and IONS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
Ca2+
P55250, -
has a small stimulatory effect
Fe
-
enzyme contains an oxygen-sensitive [4Fe-4S] cluster
Iron
-
in cells grown without aeration the Fe-S-independent enzyme form occupies over 80% of the overall fumarase. In aerobically grown cells the Fe-S-dependent fumarase occupies 80% of the overall activity; one Fe-S-dependent enzyme form and one Fe-S-independent enzyme form
Iron
-
one Fe-S-dependent enzyme form and one Fe-S-independent enzyme form
Iron
-
fumarase A contains a catalytically active [4Fe-4S]cluster
Mg2+
-, Q8NRN8
2 mM, slight stimulation
Mg2+
-
required, stimulates 10% at 5 mM
additional information
-
aluminium and gallium do not perturb the activity of fumarase C
additional information
P55250, -
no effects of Zn2+, Fe2+, or EDTA on enzyme activity
additional information
-
class II fumarase activity is frequently influenced by divalent metal ions and non-ionic surfactants. No effect by Ca2+
INHIBITORS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
(-)-citramalate
-
no inhibition by (+)-citramalate
(2R,3R)-Tartrate
-
-
(R)-malate
-, Q8NRN8
mixed-type inhibition
2-hydroxy-3-nitropropionate
-
nitronate form
2-oxoglutarate
-
-
2-Propanol
-
15-20% of maximum activity when assayed in 40% (v/v) 2-propanol
4-bromocrotonate
-
-
ammonium persulfate
-
-
ATP
-
0.35 mM, 50% inhibition
ATP
-, Q8NRN8
competitive or mixed-type inhibition
bromofumarate
-
-
chlorofumarate
-
-
chlorofumarate
-
-
cis-aconitate
-
-
citraconate
-
-
citrate
-
-
citrylpolymethylenediamine
-
-
-
CuCl2
-
inhibits 37% at 5 mM
Cyanate
-
2 mM ibuprofen and its major metabolites protect by up to 26%. Ibuprofen and the metabolites do not bind to fumarase
D-fructose
-
2 mM ibuprofen and its major metabolites protect by up to 26%. Ibuprofen and the metabolites do not bind to fumarase
D-Tartrate
-, Q8NRN8
competitive
dimethylfumarate
-
-
DL-3-phenyllactate
-
-
EDTA
-
inhibits 20% at 2.5 mM
ethanol
-
15-20% of maximum activity when assayed in 40% (v/v) ethanol
FeCl2
-
inhibits 37% at 5 mM
FeCl3
-
inhibits 47.3% at 5 mM
fumarate
P55250, -
the activity of FUMR catalyzing hydration of fumarate to L-malate is completely inhibited by 2 mM fumaric acid
glycerol
-
wild-type enzyme is inhibited due to a viscogenic effect on the recycling rate
H2O2
-
causes fibril aggregation and catalytic inactivation of fumarase
hydroxyl radical
-
causes fibril aggregation and catalytic inactivation of fumarase
iodoacetamide
-
-
iodoacetate
-
-
iodofumarate
-
-
Isocitrate
-
L-isocitrate
L-Tartrate
-
-
L-threo-hydroxyaspartate
-
-
mesaconate
-
-
meso-tartrate
-
-
meso-tartrate
-, Q8NRN8
competitive
mesotartaric acid
Q7Z1D9
competitive
methanol
-
94% of maximum activity when assayed in 40% (v/v) methanol
NaCl
-
in cells cultivated with 200 mM NaCl, the inhibition produced in fumarase is 90%
NH4Cl
-
inhibits 23% at 5 mM
phosphate
-
increases activity at less than 5 mM, competitive inhibition at higher concentrations
phosphate
-
at 0.1 mM malate and 5 mM: 14% increase in activity. At 0.1 mM malate and 50 mM phosphate: 60% inhibition. At 1 mM malate and 10 mM phosphate: 80% stimulation
potassium thiocyanate
-
IC50: 140 mM
Prednisolone
-
2 mM ibuprofen and its major metabolites have no effect on prednisolone-induced inactivation
pyromellilate
-
-
pyromellitate
-, Q8NRN8
competitive
pyromellitic acid
-
-
S-2,3-dicarboxyaziridine
-
enzyme form FUMC is inhibited, enzyme form FUMA is not inhibited
-
sulfhydryl reagents
-
-
sulfhydryl reagents
-
no inhibition
trans-aconitate
-
-
trans-aconitate
-
-
trans-glutaconate
-
-
ZnCl2
-
inhibits 55% at 5 mM
Mg2+
P55250, -
slight inhibition
additional information
-
substrate inhibition between 0.1 M and 1.0 M
-
additional information
-
no substrate inhibition by high levels of malate
-
additional information
-
inhibition by D2O arises in the recycling phase
-
additional information
-, Q8NRN8
no inactivation with L-tartrate, citrate, succinate, glycine, maleate, 1 mM iodoacetate, 1 mM iodoacetamide, 1 mM N-ethylmaleimide or 0.5 mM PCMB
-
additional information
-
during continuous L-malic acid production, enzyme inactivation, which is not complete
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
acetate
-
0.2 M, activation
arsenate
-
activates
Borate
-
activates
citrate
-
activates
phosphate
-
increases activity at less than 5 mM, competitive inhibition at higher concentrations
phosphate
-
at 0.1 mM malate and 5 mM phosphate: 14% increase in activity. At 0.1 mM malate and 50 mM phosphate: 60% inhibition. At 1 mM malate and 10 mM phosphate: 80% stimulation
selenate
-
activates
SO42-
-
activates
Cl-
-
activity increases up to 50 mM and remains constant at higher concentrations
additional information
-
activity of permeabilized cells in hydration of fumaric acid is significantly higher than that of the non-permeabilized ones
-
KM VALUE [mM]
KM VALUE [mM] Maximum
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.3
-
(S)-malate
-
pH 7.5, 70C
0.46
-
(S)-malate
P55250, -
pH 7.4, 30C, recombinant enzyme
0.59
-
(S)-malate
-
pH 7.0, 55C
1.4
-
(S)-malate
-, Q8NRN8
MES-NaOH buffer, pH 6.0
1.8
-
(S)-malate
-, Q8NRN8
MES-NaOH buffer, pH 7.0; phosphate buffer, pH 6.0
5
-
(S)-malate
-, Q8NRN8
MES-NaOH buffer, pH 7.0
6.3
-
(S)-malate
-, Q8NRN8
phosphate buffer, pH 7.0
13
-
(S)-malate
-, Q8NRN8
phosphate buffer, pH 6.0
0.145
-
acetylene dicarboxylate
-
-
0.9
-
acetylene dicarboxylate
-
-
0.11
-
bromofumarate
-
-
0.11
-
chlorofumarate
-
-
0.027
-
fluorofumarate
-
-
1.7
-
fluorofumarate
-
-
0.005
-
fumarate
-
-
0.013
-
fumarate
-
cytosolic enzyme
0.031
-
fumarate
-
-
0.125
-
fumarate
-
; pH 7.5, 70C
0.15
-
fumarate
-
enzyme form FUMA
0.25
-
fumarate
-
-
0.38
-
fumarate
-, Q8NRN8
MES-NaOH buffer, pH 7.0
0.39
-
fumarate
-
enzyme form FUMC
0.43
-
fumarate
-
pH 7.0, 55C
0.6
-
fumarate
-
fumarase A
0.67
-
fumarate
-, Q8NRN8
MES-NaOH buffer, pH 7.0
0.81
-
fumarate
-, Q8NRN8
MES-NaOH buffer, pH 6.0
1.7
-
fumarate
-
enzyme form FUMB
3.07
-
fumarate
P55250, -
pH 7.4, 30C, recombinant enzyme
3.1
-
fumarate
-, Q8NRN8
phosphate buffer, pH 6.0
3.8
-
fumarate
-, Q8NRN8
phosphate buffer, pH 7.0
4.2
-
fumarate
-, Q8NRN8
phosphate buffer, pH 6.0
8.8
-
fumarate
-
pH 7.4, 37C
0.12
-
iodofumarate
-
-
0.025
-
L-Malate
-
-
0.049
-
L-Malate
-
enzyme form FUMA
0.05
-
L-Malate
-
enzyme form FUMC
2.38
-
L-Malate
-
-
2.94
-
L-Malate
-
enzyme form FUMC
1.3
-
L-Tartrate
-
-
0.02
0.14
L-threo-chloromalate
-
-
7.5
10
L-threo-hydroxyaspartate
-
-
0.12
-
malate
-
pH 6.5, 50 mM MOPS-NaOH buffer
0.14
-
malate
-
mitochondrial enzyme
0.33
-
malate
-
pH 7.0, 50 mM MOPS-NaOH buffer
0.45
-
malate
-
-
0.63
-
malate
-
enzyme form FUMB
0.7
-
malate
-
-
0.7
-
malate
-
fumarase A
1
-
malate
-
pH 7.5, 50 mM MOPS-NaOH buffer
1.1
-
malate
-
enzyme form FUMA
1.22
-
malate
Q7Z1D9
pH 7.3, 30C, recombinant enzyme
1.4
-
malate
-
-
1.43
-
malate
Q7Z1D9
pH 7.3, 30C, worm enzyme
2
-
malate
-
pH 6.5, 50 mM potassium phosphate buffer
14
-
malate
-
pH 7.5, 50 mM potassium phosphate buffer
32
-
malate
-
pH 7.4, 37C
0.51
-
mesaconate
-
-
additional information
-
additional information
-
reaction kinetics and thermodynamics, overview
-
TURNOVER NUMBER [1/s]
TURNOVER NUMBER MAXIMUM[1/s]
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
25.2
-
(S)-malate
-
pH 7.0, 55C
34
-
(S)-malate
-, Q8NRN8
MES-NaOH buffer, pH 6.0
48
-
(S)-malate
-, Q8NRN8
phosphate buffer, pH 6.0
110
-
(S)-malate
-, Q8NRN8
MES-NaOH buffer, pH 7.0
200
-
(S)-malate
-, Q8NRN8
phosphate buffer, pH 7.0
290
-
(S)-malate
-, Q8NRN8
MES-NaOH buffer, pH 7.0
460
-
(S)-malate
-, Q8NRN8
phosphate buffer, pH 6.0
51.7
-
fumarate
-
fumarase A
219
-
fumarate
-
pH 7.0, 55C
310
-
fumarate
-, Q8NRN8
MES-NaOH buffer, pH 6.0
430
-
fumarate
-, Q8NRN8
MES-NaOH buffer, pH 7.0
510
-
fumarate
-, Q8NRN8
phosphate buffer, pH 6.0
650
-
fumarate
-, Q8NRN8
MES-NaOH buffer, pH 7.0
690
-
fumarate
-
-
720
-
fumarate
-, Q8NRN8
phosphate buffer, pH 6.0
730
-
fumarate
-, Q8NRN8
phosphate buffer, pH 7.0
1149
-
fumarate
-
pH 7.9, native enzyme
1150
-
fumarate
-
pH 7.9, native enzyme
1
-
L-Malate
-
pH 7.9, mutant enzyme E315Q
11.2
-
malate
-
fumarase A
540
-
malate
-
-
additional information
-
additional information
-
-
-
Ki VALUE [mM]
Ki VALUE [mM] Maximum
INHIBITOR
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
2.5
-
(R)-malate
-, Q8NRN8
-
16
-
D-Tartrate
-, Q8NRN8
-
0.11
-
meso-tartrate
-, Q8NRN8
-
0.077
-
mesotartaric acid
Q7Z1D9
pH 7.3, 30C
1.3
-
pyromellitate
-, Q8NRN8
-
IC50 VALUE [mM]
IC50 VALUE [mM] Maximum
INHIBITOR
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
140
-
potassium thiocyanate
-
IC50: 140 mM
SPECIFIC ACTIVITY [µmol/min/mg]
SPECIFIC ACTIVITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
173
-
-
-
205
-
-
; pH 7.5, 70C
340
-
-
FUMA
388
-
Q7Z1D9
-
450
-
-
-
721
-
-
mitochondrial enzyme
726
-
-
purified recombinant FumF, pH 8.5, 55C, substrate fumarate
730
-
-
cytosolic enzyme
730
-
-
FUMC
971
-
-
-
1047
-
-
-
2800
-
-
-
additional information
-
-
-
additional information
-
-
-
additional information
-
-
-
additional information
-
-
-
additional information
-
-
specific activity of fumarase is 2.9fold higher in SS-13BN rats
pH OPTIMUM
pH MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
6.5
-
-, Q8NRN8
phosphate buffer, substrate: fumarate
6.8
7.5
-
-
7.2
-
P55250, -
-
7.5
-
-
assay at
7.5
-
-, Q8NRN8
Tris-HCl buffer, substrate: fumarate
7.6
-
-
assay at
8
-
-
enzyme form FUMC
8.3
-
-, Q8NRN8
phosphate buffer, substrate: malate
8.5
-
-
-
8.5
-
-
enzyme form FUMA
8.5
-
-, Q8NRN8
Tris-HCl buffer, substrate: malate
additional information
-
-
at low concentrations, phosphate, sulfate, borate, selenate, arsenate and citrate activate fumarase and shift somewhat the pH optimum to a more alkaline pH
pH RANGE
pH RANGE MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
5.5
11.5
-
no activity below pH 5.5 and above pH 11.5
5.5
9
-
pH 5.5: 43% of maximal activity, pH 9.0: 70% of maximal activity
6.5
9.5
-
pH optimum at pH 8.5, the activity is dramatically suppressed below pH 7.0 and above pH 9.0
7
10
-
pH 7: about 60% of maximal activity, pH 10: about 30% of maximal activity
TEMPERATURE OPTIMUM
TEMPERATURE OPTIMUM MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
25
-
-
assay at
30
-
P55250, -
-
53
55
-
-
70
-
-
assay at
83
-
-
-
TEMPERATURE RANGE
TEMPERATURE MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
25
65
-
70% of maximum activity below 40C, and over 70% of maximum activity between 40-60C, maximal activity at approximately 55C
50
100
-
50C: about 30% of maximal activity, 100C: about 80% of maximal activity
85
95
-
85C: maximal activity, 95C: 66% of maximal activity, the enzyme is almost inactive at 40C; inactive at 40C, 85C: optimum, 95C: 66% of maximal activity
pI VALUE
pI VALUE MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
6.79
-
-
sequence calculation
7.1
-
-
isoelectric focusing
SOURCE TISSUE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
SOURCE
-
cells from individuals with hereditary leiomyomatosis and renal cell cancer have lower fumarate hydratase enzyme activity than cells from normal controls
Manually annotated by BRENDA team
Q9FI53
high level
Manually annotated by BRENDA team
Mesembryanthemum crystallinum L.
-
-
-
Manually annotated by BRENDA team
-
cells from individuals with hereditary leiomyomatosis and renal cell cancer have lower fumarate hydratase enzyme activity than cells from normal controls
Manually annotated by BRENDA team
-
loss of fumarate hydratase might be a significant event in the pathogenesis of a subset of nonsyndromic uterine leiomyomas
Manually annotated by BRENDA team
-
all missense mutations of fumarate hydratase associating with MCUL/hereditary leiomyomatosis and renal cell cancer show diminished fumarate hydratase enzymatic
Manually annotated by BRENDA team
-
biallelic inactivation of fumarate hydratase occurs in nonsyndromic uterine leiomyomas but is rare in other tumors
Manually annotated by BRENDA team
-
all missense mutations of fumarate hydratase associating with MCUL/hereditary leiomyomatosis and renal cell cancer show diminished fumarate hydratase enzymatic
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
-
the cytosolic isoenzyme and the mitochondrial isoenzyme are identical over nearly all of their amino acid sequences but differ at their N-termini
Manually annotated by BRENDA team
-
mitochondrial and cytosolic isoforms are derivatives of a single translation product and have identical amino termini
Manually annotated by BRENDA team
-
translation product of the FUM1 gene, distribution can be affected by hsp70 molecular chaperones
Manually annotated by BRENDA team
-
under normal conditions
Manually annotated by BRENDA team
-
in thin sections from kidney, liver, heart, adrenal gland and anterior pituitary, strong and specific labeling due to fumarase antibody is only detected in mitochondria. In pancreatic acinar cells, in addition to mitochondria, highly significant labeling is also observed in the zymogen granules and endoplasmic reticulum
Manually annotated by BRENDA team
-
cytosolic fumarase and mitochondrial fumarase are identical products of the same nuclear gene
Manually annotated by BRENDA team
-
the cytosolic isoenzyme and the mitochondrial isoenzyme are identical over nearly all of their amino acid sequences but differ at their N-termini
Manually annotated by BRENDA team
-
mitochondrial and cytosolic isoforms are derivatives of a single translation product and have identical amino termini
Manually annotated by BRENDA team
-
translation product of the FUM1 gene, distribution can be affected by hsp70 molecular chaperones
Manually annotated by BRENDA team
P07954
Cos-1 cells transfected with fumarase constructs, human fumarase with either the native or cytochrome c oxidase subunit VIII mitochondrial targeting sequence is detected exclusively in mitochondria in more than 98% of the cells, while the remainder 1-2% of the cells shows varying amounts of nuclear labeling. When human fumarase is fused to the yeast mitochondrial targeting sequence, more than 50% of the cells show nuclear labeling
Manually annotated by BRENDA team
-
in thin sections from kidney, liver, heart, adrenal gland and anterior pituitary, strong and specific labeling due to fumarase antibody is only detected in mitochondria. In pancreatic acinar cells, in addition to mitochondria, highly significant labeling is also observed in the zymogen granules and endoplasmic reticulum
Manually annotated by BRENDA team
-
the presequence of fumarase is exposed to the cytosol during import into mitochondria
Manually annotated by BRENDA team
-
under normal conditions
Manually annotated by BRENDA team
Mesembryanthemum crystallinum L.
-
-
-
Manually annotated by BRENDA team
P07954
Cos-1 cells transfected with fumarase constructs, human fumarase with either the native or cytochrome c oxidase subunit VIII mitochondrial targeting sequence is detected exclusively in mitochondria in more than 98% of the cells, while the remainder 1-2% of the cells shows varying amounts of nuclear labeling. When human fumarase is fused to the yeast mitochondrial targeting sequence, more than 50% of the cells show nuclear labeling
Manually annotated by BRENDA team
-
after both hydroxyurea or ionizing radiation treatments, is localized in the nucleus after DNA damage
Manually annotated by BRENDA team
-
is localized in the nucleus after DNA damage
Manually annotated by BRENDA team
-
in thin sections from kidney, liver, heart, adrenal gland and anterior pituitary, strong and specific labeling due to fumarase antibody is only detected in mitochondria. In pancreatic acinar cells, in addition to mitochondria, highly significant labeling is also observed in the zymogen granules and endoplasmic reticulum
Manually annotated by BRENDA team
PDB
SCOP
CATH
ORGANISM
Archaeoglobus fulgidus (strain ATCC 49558 / VC-16 / DSM 4304 / JCM 9628 / NBRC 100126)
Burkholderia pseudomallei (strain 1710b)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Mycobacterium abscessus (strain ATCC 19977 / DSM 44196)
Mycobacterium marinum (strain ATCC BAA-535 / M)
Mycobacterium smegmatis (strain ATCC 700084 / mc(2)155)
Rhizobium meliloti (strain 1021)
Rickettsia prowazekii (strain Madrid E)
Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
MOLECULAR WEIGHT
MOLECULAR WEIGHT MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
45000
-
P39461, -
SDS-PAGE
47900
-
P39461, -
calculated from amino acid sequence
48000
-
-
mitochondrial fumarate hydratase is translated as an approximately 54000 Da precursor, which is processed upon mitochondrial transport by cleavage of the N-terminal targeting signal, resulting in a mature form of 48000 Da
54000
-
-
mitochondrial fumarate hydratase is translated as an approximately 54000 Da precursor, which is processed upon mitochondrial transport by cleavage of the N-terminal targeting signal, resulting in a mature form of 48000 Da
64200
-
-
gel filtration
114000
-
-
gel filtration
120000
-
-
enzyme form FUMA, gel filtration
120000
-
-
gel filtration
120000
-
-
enzyme form FUMA, gel filtration
160000
-
-
sucrose density gradient centrifugation
170000
-
-
gel filtration
175000
-
-
gel filtration
180000
-
-
-
190000
-
-
gel filtration
194000
-
-
equilibrium sedimentation
195000
-
-
calculation from amino acid analysis
198000
-
-
gel filtration
200000
-
-
Fe-S-independent enzyme form, gel filtration
200000
-
-
enzyme form FUMC, gel filtration
200000
-
-
sucrose density gradient centrifugation
200000
-
-, Q8NRN8
gel filtration
440000
-
-
oligomer 1, gel filtration
600000
-
-
oligomer 2, gel filtration
SUBUNITS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
?
Q7Z1D9
x * 50502, calculation from nucleotide sequence; x * 51000, SDS-PAGE
?
-
x * 50900, about, sequence calculation, x * 43000-45000, recombinant enzyme, SDS-PAGE
?
-
x * 50900, about, sequence calculation, x * 43000-45000, recombinant enzyme, SDS-PAGE
-
dimer
-
2 * 61000, enzyme form FUMA, SDS-PAGE
dimer
-
2 * 60000, SDS-PAGE
dimer
-
2 * 60000, SDS-PAGE
dimer
-
2 * 60000, enzyme form FUMA, SDS-PAGE
tetramer
-
4 * 48000, Fe-S-independent enzyme form, SDS-PAGE
tetramer
-
4 * 50000, enzyme form FUMC, SDS-PAGE
tetramer
-
4 * 49000, SDS-PAGE in presence of 8 M urea
tetramer
-
4 * 45000
tetramer
-
4 * 48500, equilibrium sedimentation in 6 M guanidine HCl, pH 4.25
tetramer
-
4 * 45000, SDS-PAGE
tetramer
-
4 * 50000, SDS-PAGE
tetramer
-
4 * 46000, SDS-PAGE
tetramer
-
-
tetramer
-, Q8NRN8
4 * 50000, SDS-PAGE
tetramer
Sulfolobus solfataricus DSM 1616
-
4 * 45000, SDS-PAGE
-
homotetramer
-
4 * 50000, SDS-PAGE
additional information
-
a small but very important conformational change associated with the conversion of dimers to tetramers, finalizing proper orientation of active site residues
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
proteolytic modification
-
the precursor of the mitochondrial enzyme has a larger molecular weight than the mature enzyme, whereas the precursor for the cytosolic enzyme has the same molecular weight as the mature enzyme. These two precursors of fumarase are coded by two different mRNAs
Crystallization/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
free enzyme in which both sites are unoccupied by bound ligand, crystallized from a solution of 50 mM MOPS, pH 7.5, 100 mM LiSO4 and 12% PEG 4000, space group I222, X-ray data are collected between 8 and 2.19 A, unit cell parameters: a = 121.6 A, b = 128 A, c = 62.1 A
-
fumarase C
-
mutant enzyme E315Q
-
fumarase complex with meso-tartaric acid
-
native and recombinant enzyme, native fumarase is crystallized in the presence of the competitive inhibitor meso-tartrate
-
pH STABILITY
pH STABILITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
3
9
P55250, -
purified recombinant enzyme, stable
4.5
8.2
-
stable
5
9
-
stable in potassium phosphate buffer, above pH 10: dissociation into an inactive form
6
10
-
dissociation below pH 6 and above pH 10, Tris-acetate buffer
7
-
-, Q8NRN8
stable
TEMPERATURE STABILITY
TEMPERATURE STABILITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
4
-
-
half-life: 4.6 h, at 0.0438 mg of protein per ml
15
70
-
30 min, pH 8.5, activity of FumF is stable with increasing temperature below 58C in the absence of any stabilizer. When the temperature is higher than 60C, FumF protein loses almost 50% of its activity
20
-
-
half-life: 1.6 h, at 0.0438 mg of protein per ml
21
-
-, Q8NRN8
pH 7.6, stable
40
-
A5Y6J1, -
24 h, stable
45
-
P55250, -
purified recombinant enzyme, stable below
49
-
-
5 min, 50% inhibition, enzyme form FUMA
50
-
-
80 min, 30% loss of activity of the enzyme form FUMC. Rapid inactivation of enzyme form FUMA and FUMB
50
-
-
complete inactivation within several seconds
50
-
-
rapid denaturation at
51
-
-
5 min, 50% inhibition, enzyme form FUMA
70
-
-
1 h, stable
75
-
-
24 h, 10% loss of activity
85
-
-
1 h, stable
90
-
-
30 min, 72% loss of activity; 30 min, 72% of maximal activity
90
-
-
24 h, 20% loss of activity
100
-
-
30 min, complete loss of activity
GENERAL STABILITY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
exposure to air at room temperature causes 50% loss of activity, reactivation with FeSO4 and 2-mercaptoethanol
-
dithiothreitol partially restores from urea and alkaline inactivation
-, Q8NRN8
enzyme stability is achieved by addition of soy bean protein or bovine serum albumin.
-
(NH4)2SO4, protects enzyme form FUMA from inactivation at 4C
-
10% glycerol, 0.1 M KCl, 5 mM L-malate or 30% ethyleneglycol, partially protects enzyme form FUMA from inactivation at 4C
-
enzyme form FUMA, oxidation and the concomitant release of iron inactivates the enzyme in a reversible manner
-
enzyme form FUMB is extremely unstable
-
mitochondrially targeted fumarase harboring a tobacco etch virus protease recognition sequence is efficiently cleaved by the mitochondrial but not by the cytosolic tobacco etch virus protease. Fumarase is readily cleaved by cytosolic tobacco etch virus when its import into mitochondria is slowed down by either disrupting the activity of the TOMcomplex, lowering the growth temperature, or reducing the inner membrane electrochemical potential
-
50% v/v ethanol, 50% v/v methanol, 50% v/v 2-propanol, 4 M urea or 0.1% SDS, stable after treatment for 10 h at room temperature
-
0.8 M guanidine hydrochloride, 50% loss of activity after 5 min at 75C, complete inactivation at concentrations above 1.5 M
-
ORGANIC SOLVENT
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
2-propanol
-
50% (v/v), 10 h at room temperature, no significant loss of activity, slight loss of activity after 14 days
2-propanol
Sulfolobus solfataricus DSM 1616
-
50% (v/v), 10 h at room temperature, no significant loss of activity, slight loss of activity after 14 days
-
Ethanol
-
50% (v/v), 10 h at room temperature, no significant loss of activity, slight loss of activity after 14 days
Ethanol
Sulfolobus solfataricus DSM 1616
-
50% (v/v), 10 h at room temperature, no significant loss of activity, slight loss of activity after 14 days
-
Methanol
-
50% (v/v), 10 h at room temperature, no significant loss of activity, slight loss of activity after 14 days
Methanol
Sulfolobus solfataricus DSM 1616
-
50% (v/v), 10 h at room temperature, no significant loss of activity, slight loss of activity after 14 days
-
SDS
-
0.1% (v/v), 10 h at room temperature, no significant loss of activity, slight loss of activity after 14 days
SDS
Sulfolobus solfataricus DSM 1616
-
0.1% (v/v), 10 h at room temperature, no significant loss of activity, slight loss of activity after 14 days
-
urea
-
0.1% (v/v), 10 h at room temperature, no significant loss of activity, slight loss of activity after 14 days
urea
Sulfolobus solfataricus DSM 1616
-
0.1% (v/v), 10 h at room temperature, no significant loss of activity, slight loss of activity after 14 days
-
STORAGE STABILITY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
4C, under N2, stable for at least 1 month
-
4C, activity readily decreases to less than 20%
-
4C or -20C, stable for several days
-
-4C, stable for at least 6 months
-
4C, crystals in 0.55 saturated ammonium sulfate are stable for several months
-
Purification/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
-
Q7Z1D9
FUMA and FUMC
-
fumarase A
-
fumarase C
-
affinity chromatography using a column with pyromellitic acid as affinity ligand coupled to the classic Sepharose matrix
-
affinity chromatography with Sepharose derivatives containing citric acid. The purification is dependent on the length of the spacer arm, but not on the isomeric configuration of the immobilized citrate
-
Cloned/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
FUM1-green fluorescent protein (GFP) expressed driven by the 35S promoter in Arabidopsis thaliana cell cultures; FUM2-red fluorescent protein (RFP) fusions epressed by the 35S promoter, introduced into Arabidopsis thaliana cell cultures
Q9FI53
expression in Escherichia coli BL21
Q7Z1D9
a pfl ldhA double mutant Escherichia coli strain NZN11 is used to produce succinic acid by overexpressing the Escherichia coli malic enzyme gene sfcA. This strain, however, produces a large amount of malic acid as well as succinic acid. The fumB gene encoding the anaerobic fumarase of Escherichia coli is co-amplified to solve the problem of malic acid accumulation, and subsequently improve the succinic acid production
-
gene HP1325, DNA and amino acid sequence determination and analysis, expression in Escherichia coli strain BL21(DE3)
-
Cos-1 cells transfected with fumarase constructs, human fumarase with either the native or cytochrome c oxidase subunit VIII mitochondrial targeting sequence is detected exclusively in mitochondria in more than 98% of the cells, while the remainder 1-2% of the cells shows varying amounts of nuclear labeling. When human fumarase is fused to the yeast mitochondrial targeting sequence, more than 50% of the cells show nuclear labeling
P07954
expressed in HK-2 cells and in skin fibroblasts
-
expressed in yeast FUM1 mutant strain
-
expression in Escherichia coli BL21
-
entire protein-coding region of fumarase cDNA cloned from Dahl salt-sensitive, SS-13BN, and Brown Norway rats. PCR product inserted into the T-easy vector and propagated in competent Escherichia coli
-
gene fumR, overexpression in Escherichia coli strain BL21 (DE3)
P55250, -
mutant fumarase derivative lacking the MTS expressed in the FUM1 mutant strain, expressing the site-specific HO double-stranded DNA endonuclease
-
plasmid encoding fumarase lacking an MTS transformed into the wild-type, DELTAcit2 and R strains
-
expression in Escherichia coli mutant EJ1535
-
expression in Escherichia coli BL21
-
expression in Escherichia coli BL21
A5Y6J1, -
expressed in Escherichia coli strain JM109
P39461, -
gene fumF, cloned from a plasmid metagenomic library, DNA and amino acid sequence determination and analysis, sequence comparison, and phylogenetic analysis
-
EXPRESSION
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
level of FUM2 RNA in rosette leaves is higher in the light than in the dark, but total fumarase activity remains constant throughout the diurnal cycle
Q9FI53
knock down of total cellular fumarate hydratase expression using specific shRNA
-
fumarate hydratase levels increase 2fold after 24 h of treatment with double-strand breaks. Is overexpressed in response to DNA damage
-
level of fumarase mRNA is upregulated both in the DELTacit2 and wild-type plus pCit2 strains. Approximately 2fold higher Fum1 mRNA level in a DELTAcit2 strain when compared with the wild-type strain. Significant increase in fumarase expression and cellular enzymatic activity in the glyoxylate deletion strains: DELTAmls1, DELTAicl1, DELTAaco1and DELTAcit2. Succinic acid in the growth medium affects fumarase dual distribution, succinic acid directly interacts with fumarase and slows down its folding thereby causing more fumarase to be fully imported into mitochondria
-
is overexpressed in response to DNA damage
-
ENGINEERING
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
E315Q
-
mutation causes about 3% increase in Km-value for S-malate, about 20% increase in Km-value for fumarate. 10fold decrease in turnover number for S-malate, about 11fold decrease in turnover number for fumarate
H129N
-
loss of D2O inhibitory effect, product release step is accelerated by glycerol compared to inhibition of wild-type enzyme. 3.1fold reduced maximal velococity in reaction with malate, 1.13fold reduced maximal velocity in reaction with fumarate compared to wild-type enzyme
K127D
-
mutant enzyme behaves like wild-type enzyme
R126A
-
loss of D2O inhibitory effect, product release step is accelerated by glycerol compared to inhibition of wild-type enzyme. 4.3fold reduced maximal velococity in reaction with malate, 2.7fold reduced maximal velocity in reaction with fumarate compared to wild-type enzyme
R126A/H129N
-
great loss of D2O inhibitory effect, product release step is accelerated by glycerol compared to inhibition of wild-type enzyme. 8.6fold reduced maximal velococity in reaction with malate, 7.1fold reduced maximal velocity in reaction with fumarate compared to wild-type enzyme
H129N
Escherichia coli FumC
-
loss of D2O inhibitory effect, product release step is accelerated by glycerol compared to inhibition of wild-type enzyme. 3.1fold reduced maximal velococity in reaction with malate, 1.13fold reduced maximal velocity in reaction with fumarate compared to wild-type enzyme
-
K127D
Escherichia coli FumC
-
mutant enzyme behaves like wild-type enzyme
-
R126A
Escherichia coli FumC
-
loss of D2O inhibitory effect, product release step is accelerated by glycerol compared to inhibition of wild-type enzyme. 4.3fold reduced maximal velococity in reaction with malate, 2.7fold reduced maximal velocity in reaction with fumarate compared to wild-type enzyme
-
R126A/H129N
Escherichia coli FumC
-
great loss of D2O inhibitory effect, product release step is accelerated by glycerol compared to inhibition of wild-type enzyme. 8.6fold reduced maximal velococity in reaction with malate, 7.1fold reduced maximal velocity in reaction with fumarate compared to wild-type enzyme
-
A117P
-
missense mutation
A239T
-
missense mutation
A274T
-
missense mutation
A308Y
-
the mutation is associated with fumarase deficiency
A385D
-
missense mutation
C333Y
-
missense mutation
D425V
-
the mutation is associated with fumarase deficiency
E319Q
-
mutant with strongly reduced activity
E355K
-
missense mutation
E362Q
-
the mutation is associated with fumarase deficiency
F312C
-
the mutation is associated with fumarase deficiency
G282V
-
missense mutation
G397R
-
missense mutation
H135R
-
missense mutation
H180R
-
missense mutation
H318L
-
the mutation is associated with fumarase deficiency
H402C
-
the mutation is associated with fumarase deficiency
I229T
-
missense mutation
I77V
-
the mutant enzyme shows increased activity
K230R
-
missense mutation
K424R
-
the activity of the mutated protein is significantly reduced as compared to wild type
K424R
-
missense mutation
K467R
-
missense mutation
L335P
-
missense mutation
L507P
-
missense mutation
M195T
-
missense mutation
M368T
-
the mutation is associated with hereditarymultiplecutaneous leiomyoma
N107T
-
missense mutation
N188S
-
missense mutation
N310Y
-
missense mutation
N330S
-
missense mutation detected in a patient with a bilateral renal cell cancer
N340K
-
missense mutation
N362K
-
the mutation is associated with renal cell cancer
P174R
-
missense mutation
P192L
-
missense mutation
P369S
-
the mutation is associated with fumarase deficiency
Q142K
-
missense mutation
Q185R
-
missense mutation
Q376P
-
the mutation is associated with fumarase deficiency
Q439P
-
the mutation is associated with renal cell cancer
R101P
-
the mutation is associated with renal cell cancer
R101X
-
the mutation is associated with renal cell cancer
R160G
-
missense mutation
R190H
-
the mutation is associated with renal cell cancer
R190H
-
almost inactive mutant, the R190H missense mutation is the most frequent in hereditary leiomyomatosis and renal cell cancer patients
R233C
-
the mutation is associated with renal cell cancer
R233H
-
the mutation is associated with renal cell cancer
R233L
-
the mutation is associated with renal cell cancer
R343X
-
the mutation is associated with renal cell cancer
R51E
-
missense mutation
S158I
-
missense mutation
S187L
-
missense mutation
S334R
-
the mutation is associated with hereditarymultiplecutaneous leiomyoma
S365G
-
missense mutation
S365N
-
missense mutation
S41P
-
the mutation is associated with renal cell cancer
T330P
-
missense mutation
V322D
-
missense mutation
V394L
-
missense mutation
Y465C
-
missense mutation
A347S
-
mutation results in an increase in optimum temperature of 10C and a fourfold enhancement in specific activity
G163R
-
mutation results in an increase in optimum temperature of 5C
G163R/G170E
-
mutant is more thermostable than wild-type scFUMC. Mutation results in an increase in optimum temperature of 5C
G163R/G170E/A347S
-
mutant is more thermostable than wild-type scFUMC. Mutation results in an increase in optimum temperature of 5C
G170E
-
mutation results in an increase in optimum temperature of 5C
G170E/A347S
-
mutation results in an increase in optimum temperature of 5C
M454I
-
missense mutation
additional information
-
E319Q mutation, an inborn error of fumarase causes progressive psychomotor retardation, failure to thrive, microcephaly and abnormal posture with hypotonia contrasting with hypertonia of limbs
additional information
-
hereditary leiomyomatosis and renal cell cancer is a hereditary cancer syndrome predisposing individuals to the development of aggressive kidney cancer. These individuals harbour a germline mutation of fumarate hydratase
H153R
-
is catalytically inactive since it does not complement a fumarase knockout strain with respect to its TCA cycle function. Yeast strains expressing the mutant protein do not grow on glycerol as the sole energy and carbon source
additional information
-
isolation of fumarase mutants in which dual targeting (to cytosol and mitochondria) is abolished because of perturbation of its conformation
APPLICATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
synthesis
-
production of (S)-malic acid, which is used as an acidurant in fruit and vegetable juices, carbonated soft drinks, jams and candies, in amino acid infusions and for the treatment of hepatic malfunctioning
synthesis
-
economic production of L-malate in an enzyme membrane reactor
synthesis
-
a pfl ldhA double mutant Escherichia coli strain NZN11 is used to produce succinic acid by overexpressing the Escherichia coli malic enzyme gene sfcA. This strain, however, produces a large amount of malic acid as well as succinic acid. The fumB gene encoding the anaerobic fumarase of Escherichia coli is co-amplified to solve the problem of malic acid accumulation, and subsequently improve the succinic acid production
analysis
-
fumarate hydratase activity can be useful in the diagnosis of hereditary leiomyomatosis and renal cell cancer in cases with atypical presentation and undetectable fumarate hydratase mutations. Furthermore, fumarate hydratase activity testing is of value in laboratory investigations to elucidate the mechanism of hereditary leiomyomatosis and renal cell cancer
medicine
-
fumarate immunohistochemistry may serve as a useful low-cost screening method to identify hereditary leiomyomatosis and renal cancer
medicine
-
fumarate hydratase activity can be useful in the diagnosis of hereditary leiomyomatosis and renal cell cancer in cases with atypical presentation and undetectable fumarate hydratase mutations. Furthermore, fumarate hydratase activity testing is of value in laboratory investigations to elucidate the mechanism of hereditary leiomyomatosis and renal cell cancer
medicine
-
whole-gene fumarate hydratase deletions are not a frequent cause of hereditary leiomyomatosis and renal cell cancer syndrome
industry
-
use of purified enzyme in L-malic acid production is uneconomical because whole cells are cheaper. Use of one mg of purified fumarase in continuous production of L-malic acids, corresponds to the use of enzyme in 68 g (wet weight) cells of Saccharomyces bayanus or in 120 g (wet weight) cells of baker's yeast
synthesis
A5Y6J1, -
stFUMC is a highly efficient, thermostable fumarase C with industrial potential
industry
-
use of purified enzyme in L-malic acid production is uneconomical because whole cells are cheaper. Use of one mg of purified fumarase in continuous production of L-malic acids, corresponds to the use of enzyme in 68 g (wet weight) cells of Saccharomyces bayanus or in 120 g (wet weight) cells of baker's yeast
medicine
-
metabolites of ibuprofen may play a role in its anti-cataract effect by protecting lenticular enzymes
synthesis
-
highly stable enzyme would be ideal for use in various industrial processes, especially since the specific activity is also very high
synthesis
-
fumarase is used for the industrial production of L-malate from the substrate fumarate