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Information on EC 4.2.1.2 - fumarate hydratase and Organism(s) Escherichia coli and UniProt Accession P05042
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4.2.1.2 fumarate hydrataseSpecify your search results
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- 4.2.1.2
- succinate
- leiomyomatosis
- hereditary
-
tricarboxylic
- uterine
- leiomyoma
-
hlrcc
-
germline
- isocitrate
- citrate
- tca
-
papillary
-
krebs
- aconitase
- carboxylase
-
citric
-
predisposition
- fibroids
- phosphoenolpyruvate
- succinyl-coa
- nucleoli
-
l-malic
-
halo
- alpha-ketoglutarate
- leiomyosarcoma
-
oncometabolite
- paragangliomas
- aspartase
-
pseudohypoxic
-
reed
- oxalacetate
-
perinucleolar
-
hippel-lindau
-
hysterectomy
-
chromophobe
-
1.1.1.37
- analysis
- 2-hydroxyglutarate
- synthesis
-
papules
- oncocytomas
- medicine
- industry
The taxonomic range for the selected organisms is: Escherichia coli
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota, Archaea
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota, Archaea
Synonyms
fumarase, fumarate hydratase, fumarase c, class ii fumarase, lmfh-2, scfumc, slfumc, mmcbc, lmfh-1, stfumc, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
FumA
fumarase
-
-
-
-
FumB
hydratase, fumarate
-
-
-
-
L-malate hydro-lyase
-
-
-
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
elimination
-
-
-
-
PATHWAY SOURCE
PATHWAYS
KEGG
-
-, -, -, -, -, -, -, -, -, -, -, -, -, -, -, -, -, -
SYSTEMATIC NAME
IUBMB Comments
(S)-malate hydro-lyase (fumarate-forming)
-
CAS REGISTRY NUMBER
COMMENTARY
9032-88-6
-
SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
fumarate + H2O
(S)-malate
the catalytic efficiency of FumA with (S)-citramalate/mesaconate is about 4% of that with fumarate or (S)-malate
-
-
r
(S)-citramalate
mesaconate + H2O
the catalytic efficiency of FumA with (S)-citramalate/mesaconate is about 4% of that with fumarate or (S)-malate
-
-
r
(S)-malate
fumarate + H2O
-
-
wild-type enzyme is rate-limited in the recycling of free enzyme isoforms that follows product release
?
(S)-malate
fumarate + H2O
the catalytic efficiency of FumA with (S)-citramalate/mesaconate is about 4% of that with fumarate or (S)-malate
-
-
r
fumarate + H2O
L-malate
-
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
-
?
mesaconate + H2O
(S)-citramalate
the catalytic efficiency of FumA with (S)-citramalate/mesaconate is about 4% of that with fumarate or (S)-malate
-
-
r
additional information
?
-
enzyme is a promiscuous mesaconase/fumarase with a 2- to 3fold preference for mesaconate over fumarate
-
-
?
additional information
?
-
enzyme is a promiscuous mesaconase/fumarase with a 2- to 3fold preference for mesaconate over fumarate
-
-
?
additional information
?
-
enzyme is a promiscuous mesaconase/fumarase with a 2- to 3fold preference for mesaconate over fumarate
-
-
?
additional information
?
-
enzyme is a promiscuous mesaconase/fumarase with a 2- to 3fold preference for mesaconate over fumarate
-
-
?
additional information
?
-
-
enzyme is a promiscuous mesaconase/fumarase with a 2- to 3fold preference for mesaconate over fumarate
-
-
?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
fumarate + H2O
L-malate
-
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
-
?
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Iron
additional information
Iron
-
one Fe-S-dependent enzyme form and one Fe-S-independent enzyme form
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
additional information
activity does not increase upon incubation with Fe2+
additional information
activity does not increase upon incubation with Fe2+
additional information
activity does not increase upon incubation with Fe2+
additional information
activity does not increase upon incubation with Fe2+
additional information
-
activity does not increase upon incubation with Fe2+
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
glycerol
-
wild-type enzyme is inhibited due to a viscogenic effect on the recycling rate
S-2,3-dicarboxyaziridine
-
enzyme form FUMC is inhibited, enzyme form FUMA is not inhibited
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
37
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
PDB
SCOP
CATH
UNIPROT
ORGANISM
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
120000
200000
60000
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
dimer
tetramer
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
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
PROTEIN VARIANTS
ORGANISM
UNIPROT
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
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
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
50
-
80 min, 30% loss of activity of the enzyme form FUMC. Rapid inactivation of enzyme form FUMA and FUMB
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
10% glycerol, 0.1 M KCl, 5 mM L-malate or 30% ethyleneglycol, partially protects enzyme form FUMA from inactivation at 4°C
-
enzyme form FUMA, oxidation and the concomitant release of iron inactivates the enzyme in a reversible manner
-
OXIDATION STABILITY
ORGANISM
UNIPROT
LITERATURE
the enzyme remains stable under oxic conditions
749072
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
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
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Yumoto, N.; Tokushige, M.
Characterization of multiple fumarase proteins in Escherichia coli
Biochem. Biophys. Res. Commun.
153
1236-1243
1988
Escherichia coli
Woods, S.A.; Schwartzbach, S.D.; Guest, J.R.
Two biochemically distinct classes of fumarase in Escherichia coli
Biochim. Biophys. Acta
954
14-26
1988
Escherichia coli
Weaver, T.M.; Levitt, D.G.; Banaszak, L.J.
Purification and crystallization of fumarase C from Escherichia coli
J. Mol. Biol.
231
141-144
1993
Escherichia coli
Ueda, Y.; Yumoto, N.; Tokushige, M.; Fukui, K.; Ohya-Nishiguchi, H.
Purification and characterization of two types of fumarase from Escherichia coli
J. Biochem.
109
728-733
1991
Escherichia coli
Flint, D.H.; Emptage, M.H.; Guest, J.R.
Fumarase a from Escherichia coli: purification and characterization as an iron-sulfur cluster containing enzyme
Biochemistry
31
10331-10337
1992
Escherichia coli
Flint, D.H.
Initial kinetic and mechanistic characterization of Escherichia coli fumarase A
Arch. Biochem. Biophys.
311
509-516
1994
Escherichia coli
Tseng, C.P.; Yu, C.C.; Lin, H.H.; Chang, C.Y.; Kuo, J.T.
Oxygen- and growth rate-dependent regulation of Escherichia coli fumarase (FumA, FumB, and FumC) activity
J. Bacteriol.
183
461-467
2001
Escherichia coli
Rose, I.A.; Weaver, T.M.
The role of the allosteric B site in the fumarase reaction
Proc. Natl. Acad. Sci. USA
101
3393-3397
2004
Escherichia coli, Escherichia coli FumC
Estevez, M.; Skarda, J.; Spencer, J.; Banaszak, L.; Weaver, T.M.
X-ray crystallographic and kinetic correlation of a clinically observed human fumarase mutation
Protein Sci.
11
1552-1557
2002
Homo sapiens, Escherichia coli (P05042), Escherichia coli
Weaver, T.
Structure of free fumarase C from Escherichia coli
Acta Crystallogr. Sect. D
61
1395-1401
2005
Escherichia coli (P05042), Escherichia coli
Hong, S.H.; Lee, S.Y.
Enhanced production of succinic acid by metabolically engineered Escherichia coli with amplified activities of malic enzyme and fumarase
Biotechnol. Bioprocess Eng.
9
252-255
2004
Escherichia coli
-
van Vugt-Lussenburg, B.M.; van der Weel, L.; Hagen, W.R.; Hagedoorn, P.L.
Biochemical similarities and differences between the catalytic [4Fe-4S] cluster containing fumarases FumA and FumB from Escherichia coli
PLoS ONE
8
e55549
2013
Escherichia coli
Kronen, M.; Berg, I.A.
Mesaconase/Fumarase FumD in Escherichia coli O157 H7 and promiscuity of Escherichia coli class I fumarases FumA and FumB
PLoS ONE
10
e0145098
2015
Escherichia coli (P05042), Escherichia coli (P0AC33), Escherichia coli (P14407), Escherichia coli (Q8X999), Escherichia coli, Escherichia coli K-12 (P14407), Escherichia coli K-12 W3110 / K-12 (P14407), Escherichia coli O157:H7, Escherichia coli O157:H7 ATCC 700728, Escherichia coli W3110 / K-12 (P05042), Escherichia coli W3110 / K-12 (P0AC33)
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