Information on EC 1.1.1.85 - 3-isopropylmalate dehydrogenase

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

EC NUMBER
COMMENTARY hide
1.1.1.85
-
RECOMMENDED NAME
GeneOntology No.
3-isopropylmalate dehydrogenase
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
(2R,3S)-3-isopropylmalate + NAD+ = (2S)-2-isopropyl-3-oxosuccinate + NADH + H+
show the reaction diagram
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
oxidation
-
-
-
-
redox reaction
-
-
-
-
reduction
-
-
-
-
PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
Biosynthesis of secondary metabolites
-
-
butanol and isobutanol biosynthesis (engineered)
-
-
C5-Branched dibasic acid metabolism
-
-
Metabolic pathways
-
-
Valine, leucine and isoleucine biosynthesis
-
-
isoleucine metabolism
-
-
leucine metabolism
-
-
SYSTEMATIC NAME
IUBMB Comments
(2R,3S)-3-isopropylmalate:NAD+ oxidoreductase
The product decarboxylates spontaneously to yield 4-methyl-2-oxopentanoate.
CAS REGISTRY NUMBER
COMMENTARY hide
9030-97-1
-
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
No 1023
-
-
Manually annotated by BRENDA team
No 1023
-
-
Manually annotated by BRENDA team
gene leuB
SwissProt
Manually annotated by BRENDA team
-
SwissProt
Manually annotated by BRENDA team
gene leu2A
SwissProt
Manually annotated by BRENDA team
-
SwissProt
Manually annotated by BRENDA team
no 38-2
-
-
Manually annotated by BRENDA team
Bacillus sp. no 38-2
no 38-2
-
-
Manually annotated by BRENDA team
gene leuB
SwissProt
Manually annotated by BRENDA team
-
SwissProt
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
gene leu2
SwissProt
Manually annotated by BRENDA team
strain C175/CBS 8195, gene LEU2
SwissProt
Manually annotated by BRENDA team
strain C175/CBS 8195, gene LEU2
SwissProt
Manually annotated by BRENDA team
gene leu2
SwissProt
Manually annotated by BRENDA team
TIT 01010
-
-
Manually annotated by BRENDA team
M588
-
-
Manually annotated by BRENDA team
i.e. Eremothecium gossypii, gene leu2
SwissProt
Manually annotated by BRENDA team
gene leuB
SwissProt
Manually annotated by BRENDA team
gene leuB
SwissProt
Manually annotated by BRENDA team
gene leu2
SwissProt
Manually annotated by BRENDA team
strain SK103
-
-
Manually annotated by BRENDA team
gene leu2
SwissProt
Manually annotated by BRENDA team
gene leuB
SwissProt
Manually annotated by BRENDA team
strain I5
-
-
Manually annotated by BRENDA team
strain I5
-
-
Manually annotated by BRENDA team
i.e. Septoria tritici, gene leuC
SwissProt
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
physiological function
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
(2R,3S)-3-isopropylmalate + NAD+
(2S)-2-isopropyl-3-oxosuccinate + NADH + H+
show the reaction diagram
(2R,3S)-3-isopropylmalate + NAD+
2-ketoisocaproate + NADH + CO2
show the reaction diagram
-
-
-
-
?
(2R,3S)-3-isopropylmalate + NAD+
2-oxoisocaproate + NADH + CO2
show the reaction diagram
(2R,3S)-3-isopropylmalate + NAD+
2-oxoisocaproate + NADH + H+ + CO2
show the reaction diagram
-
-
-
-
?
(2R,3S)-3-isopropylmalate + NAD+
4-methyl-2-oxovalerate + CO2 + NADH + H+
show the reaction diagram
-
-
-
?
(2R,3S)-3-isopropylmalate + NAD+
?
show the reaction diagram
(2R,3S)-3-isopropylmalate + NAD+
D-3-isopropyl-2-oxosuccinate + NADH + H+
show the reaction diagram
(2R,3S)-3-isopropylmalate + NAD+
isopropyl-3-oxosuccinate + NADH + H+
show the reaction diagram
-
-
-
r
(2R,3S)-3-isopropylmalate + thionicotinamide NAD+
2-oxoisohexanoate + thionicotinamideNADH + CO2
show the reaction diagram
(S)-malate + NAD+
pyruvate + NADH + CO2
show the reaction diagram
-
12% of the activity with 3-isopropylmalate
-
-
?
3-(2'-methylthio)ethylmalate + NAD+
? + NADH + H+
show the reaction diagram
-
-
-
?
3-ethylmalate + NAD+
3-ethylpyruvate + NADH + CO2
show the reaction diagram
3-isoamylmalate + NAD+
3-isoamylpyruvate + NADH + CO2
show the reaction diagram
-
-
-
-
?
3-isopropylmalate + NAD+
2-ketoisocaproate + CO2 + NADH + H+
show the reaction diagram
3-isopropylmalate + NAD+
2-ketoisocaproate + NADH + CO2
show the reaction diagram
3-isopropylmalate + NAD+
?
show the reaction diagram
-
-
-
-
?
3-methylmalate + NAD+
3-methylpyruvate + NADH + CO2
show the reaction diagram
-
-
-
-
?
3-tert-butylmalate + NAD+
3-tert-butylpyruvate + NADH + CO2
show the reaction diagram
-
-
-
-
?
beta-methylmalate + NAD+
2-oxobutyrate + NADH + CO2
show the reaction diagram
-
enzyme catalyzes the final step in the pyruvate pathway to 2-oxobutyrate
-
-
?
D-3-ethylmalate + NAD+
D-3-ethyl-2-oxosuccinate + NADH + H+
show the reaction diagram
D-3-isobutylmalate + NAD+
D-3-isobutyl-2-oxosuccinate + NADH + H+
show the reaction diagram
D-3-isopentylmalate + NAD+
D-3-isopentyl-2-oxosuccinate + NADH + H+
show the reaction diagram
D-3-methylmalate + NAD+
D-3-methyl-2-oxosuccinate + NADH + H+
show the reaction diagram
-
-
-
?
D-3-t-butylmalate + NAD+
D-3-t-butyl-2-oxosuccinate + NADH + H+
show the reaction diagram
-
-
-
?
D-malate + NAD+
pyruvate + NADH + CO2
show the reaction diagram
DL-3-isopropylmalate + NAD+
DL-isopropyl-3-oxosuccinate + NADH + H+
show the reaction diagram
-
-
-
-
?
ethylmalate + NAD+
ethylpyruvate + NADH + CO2
show the reaction diagram
-
-
-
-
?
homoisocitrate + NAD+
? + NADH + H+
show the reaction diagram
isopropylmalate + NAD+
?
show the reaction diagram
-
-
-
-
?
malate + NAD+
3-oxosuccinate + NADH + H+
show the reaction diagram
-
-
-
?
malate + NAD+
pyruvate + NADH + CO2
show the reaction diagram
malate + NADP+
pyruvate + NADPH + CO2
show the reaction diagram
-
-
-
-
?
tartrate + NAD+
?
show the reaction diagram
-
-
-
-
?
tartrate + NADP+
?
show the reaction diagram
-
-
-
-
?
tert-butylmalate + NAD+
tert-butylpyruvate + NADH + CO2
show the reaction diagram
-
-
-
-
?
threo-D-3-isopropylmalate + NAD+
?
show the reaction diagram
threo-DL-isopropylmalate + NAD+
2-isopropyl-3-oxosuccinate + NADH
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
(2R,3S)-3-isopropylmalate + NAD+
(2S)-2-isopropyl-3-oxosuccinate + NADH + H+
show the reaction diagram
(2R,3S)-3-isopropylmalate + NAD+
2-oxoisocaproate + NADH + CO2
show the reaction diagram
(2R,3S)-3-isopropylmalate + NAD+
4-methyl-2-oxovalerate + CO2 + NADH + H+
show the reaction diagram
P93882
-
-
-
?
(2R,3S)-3-isopropylmalate + NAD+
?
show the reaction diagram
P50455
the enzyme is enzyme involved in leucine biosynthesis
-
-
?
3-isopropylmalate + NAD+
2-ketoisocaproate + CO2 + NADH + H+
show the reaction diagram
-
the enzyme catalyzes a step in leucine biosynthesis
-
-
?
additional information
?
-
-
the enzyme catalyzes a step in leucine biosynthesis
-
-
-
COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
NADP+
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Ca2+
-
0.5 mM, very minor stimulatory effect
Fe2+
-
0.5 mM, very minor stimulatory effect
Rb+
-
RbCl enhances activity
Zn2+
-
0.5 mM, very minor stimulatory effect
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
(2S,3S)-3-methylmercaptomalate
-
strong competitive inhibitor
-
1,2-Cyclohexanediamine-N,N,N',N'-tetraacetate
-
-
Fe2+
-
0.5 mM, 41% inhibition
iodoacetamide
iodoacetate
isocitrate
-
-
NaCl
-
250 mM, 48% inhibition
NADH
-
NADH always produces competitive inhibition patterns with respect to NAD and noncompetitive inhibition patterns with respect to the substrates
O-isobutenyloxalylhydroxamate
O-isobutenyloxalylhydroxamate binds to the active site of enzyme in a mode similar to the substrate isopropylmalate
p-hydroxymercuribenzoate
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0035 - 3.73
(2R,3S)-3-isopropylmalate
0.045 - 0.502
3-(2'-methylthio)ethylmalate
0.013
3-ethylmalate
-
-
0.11
3-isoamylmalate
-
-
0.0039 - 0.026
3-isopropylmalate
0.05
3-methylmalate
-
-
0.074
3-tert-butylmalate
-
-
0.0011
D-3-ethylmalate
pH 8.0
0.0015
D-3-isobutylmalate
pH 8.0
0.0058
D-3-isopentylmalate
pH 8.0
0.0012 - 0.0267
D-3-isopropylmalate
0.0037
D-3-methylmalate
pH 8.0
0.0023
D-3-t-butylmalate
pH 8.0
0.41 - 4
D-malate
0.002 - 0.0133
DL-3-isopropylmalate
0.019
dl-erythro-beta-ethylmalate
-
pH 9.0, 22°C
0.0092
erythro-Lg-beta-isopropylmalate
-
pH 9.0, 22°C
-
0.09
ethylmalate
-
pH 7.6
5.9
homoisocitrate
at pH 8.0 and 60°C
0.000017 - 0.316
isopropylmalate
12
L-malate
-
pH 9.0
0.0326 - 35.59
malate
0.00321 - 3.56
NAD+
0.014 - 6.579
NADP+
0.105
propylmalate
-
pH 7.6
0.0407 - 1.21
Tartrate
0.214
tert-butylmalate
-
pH 7.6
0.051
thionicotinamide-NAD+
-
pH 9.0, 22°C
0.0061 - 0.0161
threo-D,L-isopropylmalate
0.08
threo-Ds-3-Isopropylmalate
-
60°C
additional information
additional information
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0025 - 48.1
(2R,3S)-3-isopropylmalate
0.016 - 0.85
3-(2'-methylthio)ethylmalate
38
3-ethylmalate
Acidithiobacillus ferrooxidans
-
-
20
3-isoamylmalate
Acidithiobacillus ferrooxidans
-
-
3.8 - 28
3-isopropylmalate
28
3-methylmalate
Acidithiobacillus ferrooxidans
-
-
2.7
3-tert-butylmalate
Acidithiobacillus ferrooxidans
-
-
3.1
D-3-ethylmalate
Sulfolobus tokodaii
P50455
pH 8.0
3.1
D-3-isobutylmalate
Sulfolobus tokodaii
P50455
pH 8.0
2.7
D-3-isopentylmalate
Sulfolobus tokodaii
P50455
pH 8.0
2.36 - 117
D-3-isopropylmalate
3.5
D-3-methylmalate
Sulfolobus tokodaii
P50455
pH 8.0
0.96
D-3-t-butylmalate
Sulfolobus tokodaii
P50455
pH 8.0
70
ethylmalate
Escherichia coli
-
pH 7.6
0.26
homoisocitrate
Sulfolobus acidocaldarius
Q4JB37
at pH 8.0 and 60°C
0.09 - 69
isopropylmalate
0.19 - 10.6
malate
0.15 - 117
NAD+
0.09 - 4.69
NADP+
0.1 - 0.26
Tartrate
6
tert-butylmalate
Escherichia coli
-
pH 7.6
additional information
additional information
Thermus thermophilus
-
the cold adaption results from the destabilization of the ternary complex caused by increase in the volume of the residue at position 126
-
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.009 - 1700
(2R,3S)-3-isopropylmalate
1131
0.038 - 18.77
3-(2'-methylthio)ethylmalate
5879
440
homoisocitrate
Sulfolobus acidocaldarius
Q4JB37
at pH 8.0 and 60°C
1871
0.12 - 190
NAD+
7
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.000062
(2S,3S)-3-methylmercaptomalate
-
pH 7.8, 60°C
-
additional information
additional information
-
-
-
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
0.54
-
slow electrophoretic form
4.7
-
mutant E253A
5.2
-
mutant E253W
5.9
-
mutant E253G
7
-
mutant E253Q
7.4
-
mutant E253I
7.6
-
mutant E253F; mutant E253L
9
-
mutant E253V
13.9
-
wild-type
19.4
-
55°C; pH 7.0, 55°C
additional information
pH RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7.5 - 11.5
-
about 75% of maximal activity at pH 7.5 and 11.5
8 - 10.1
-
pH 8.0: 75% of maximal activity, pH 8.9-10.1: optimum
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
40
-
assay at
50 - 55
55
-
assay at
96
Tm-value of wild-type enzyme is 96°C. Tm-value of mutant enzyme K152R is 95.6°C. Tm-value of mutant enzyme (M91L/I95L/K152R/G154A/A259S/F261P/Y282L) is 96.4°C
97
Tm-value of mutant enzyme A259S/F261P is 97.1°C; Tm-value of mutant enzyme K152R/G154A is 97.2°C
98
Tm-value of mutant enzyme G154A is 97.9°C
99
t1/2: 3.67 min (wild-type enzyme), 5.52 min (mutant enzyme M91L/I95L), 6.56 min (K152R/G154A mutant enzyme), 5.72 min (K152R mutant enzyme), 7.13 min (G154A mutant enzyme), 4.79 min (A259S/F261P mutant enzyme), 3.79 min (Y282L mutant enzyme), 6.5 min (M91L/I95L/K152R/G154A/A259S/F261P/Y282L mutant enzyme); Tm-value of mutant enzyme M91L/I95L is 99.2°C
additional information
-
reaction temperature dependence, overview
TEMPERATURE RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
20 - 40
-
the van ’t Hoff plot of Km IPM shows sigmoid-like transition within this range
25 - 95
2% of maximal activity at 25°C, maximal activity at 95°C
40 - 80
-
40°C: about 45% of maximal activity, 80°C: about 85% of maximal activity
pI VALUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
6.9
-
isoelectric focusing
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
-
high expression level of IMD3 and IMD2
Manually annotated by BRENDA team
-
very low expression level of IMD1
Manually annotated by BRENDA team
-
high expression level of IMD1 and IMD2
Manually annotated by BRENDA team
-
high expression level of IMD3 and IMD2
Manually annotated by BRENDA team
additional information
-
tissue specific expression of genes IMD1, IMD2, and IMD3, overview
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
-
the enzyme contains a transit peptide
Manually annotated by BRENDA team