Information on EC 1.1.1.286 - isocitrate-homoisocitrate dehydrogenase

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

EC NUMBER
COMMENTARY hide
1.1.1.286
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RECOMMENDED NAME
GeneOntology No.
isocitrate-homoisocitrate dehydrogenase
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
(1R,2S)-1-hydroxybutane-1,2,4-tricarboxylate + NAD+ = 2-oxoadipate + CO2 + NADH + H+
show the reaction diagram
isocitrate + NAD+ = 2-oxoglutarate + CO2 + NADH
show the reaction diagram
PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
coenzyme B biosynthesis
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L-lysine biosynthesis IV
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L-lysine biosynthesis V
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lysine metabolism
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Citrate cycle (TCA cycle)
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Lysine biosynthesis
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Metabolic pathways
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Biosynthesis of secondary metabolites
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Microbial metabolism in diverse environments
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Biosynthesis of antibiotics
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SYSTEMATIC NAME
IUBMB Comments
isocitrate(homoisocitrate):NAD+ oxidoreductase (decarboxylating)
Requires Mn2+ and K+ or NH4+ for activity. Unlike EC 1.1.1.41, isocitrate dehydrogenase (NAD+) and EC 1.1.1.87, homoisocitrate dehydrogenase, this enzyme, from Pyrococcus horikoshii, can use both isocitrate and homoisocitrate as substrates. The enzyme may play a role in both the lysine and glutamate biosynthesis pathways.
CAS REGISTRY NUMBER
COMMENTARY hide
9001-58-5
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9067-90-7
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ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
expression in Escherichia coli
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Manually annotated by BRENDA team
strain HB27, expression in Escherichia coli
Swissprot
Manually annotated by BRENDA team
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
(1R,2S)-1-hydroxybutane-1,2,4-tricarboxylate + NAD+
2-oxoadipate + CO2 + NADH + H+
show the reaction diagram
-
chemical mechanism, stereochemistry of hydride transfer to NAD, overview
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-
?
3-isopropylmalate + NAD+
?
show the reaction diagram
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at 0.1% of the rate with homoisocitrate
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?
homoisocitrate + NAD+
? + NADH
show the reaction diagram
isocitrate + NAD+
2-oxoglutarate + CO2 + NADH
show the reaction diagram
isocitrate + NADP+
2-oxoglutarate + CO2 + NADPH
show the reaction diagram
additional information
?
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
homoisocitrate + NAD+
? + NADH
show the reaction diagram
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-
-
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?
additional information
?
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the enzyme catalyzes the fourth reaction of the alpha-aminoadipate pathway for lysine biosynthesis, the conversion of homoisocitrate to alpha-ketoadipate using NAD+ as an oxidizing agent
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COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Mg2+
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divalent cation required, Mg2+ is preferred over Mn2+
Mn2+
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divalent cation required, Mg2+ is preferred over Mn2+, inhibitory above 1 mM
NH4+
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200 mM activates by 80.9%
Rb+
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200 mM activates by 29.3%
additional information
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200 mM Cs+, Li+, and Na+ do not activate
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
3-carboxypropylidenemalate
homoisocitrate
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competitive, pH-dependent substrate inhibition
isocitrate
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competitive, pH-dependent substrate inhibition
K+
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absolute requirement, inhibitory above 0.4 M
Mn2+
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inhibitory above 1 mM
NADH
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product inhibitor
NH4+
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may substitute for K+, inhibitory above 0.2 M
potassium acetate
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
1.33
3-isopropylmalate
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30C, pH 7.8, wild-type
0.0183 - 7.486
homoisocitrate
0.0164 - 0.465
isocitrate
0.0771 - 0.193
NAD+
additional information
additional information
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kinetic mechanism, detailed overview
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TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.371
3-isopropylmalate
Deinococcus radiodurans
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30C, pH 7.8, wild-type
5.46 - 171
homoisocitrate
10.9 - 171
isocitrate
21.8 - 30.3
NAD+
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.043
3-carboxypropylidenemalate
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pH 8.0, 25C, versus homoisocitrate
500
potassium acetate
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pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
pH RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
5 - 10
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pH-profile, overview
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
154000
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gel filtration
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
tetramer
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
90
half-life 16.7 h
Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
recombinant enzyme expressed in Escherichia coli, purification of inclusion bodies requires N-laurylsarcosine
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Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
expression in Escherichia coli
ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
R85V
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increased ability to use 3-isopropylmalate
R87T
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uses substrate homoisocitrate, but not substrates isocitrate or 3-isopropylmalate
R87V
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uses substrate homoisocitrate, but not substrates isocitrate or 3-isopropylmalate
R85V
complete loss of activity with citrate, retains activity with isocitrate
additional information
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deletion of A80, inability of mutant to use 3-isopropylmalate, isocitrate is 4fold preferred over homoisocitrate