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Information on EC 1.1.1.85 - 3-isopropylmalate dehydrogenase and Organism(s) Escherichia coli and UniProt Accession P30125

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IUBMB Comments
The product decarboxylates spontaneously to yield 4-methyl-2-oxopentanoate.
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This record set is specific for:
Escherichia coli
UNIPROT: P30125
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Word Map
The taxonomic range for the selected organisms is: Escherichia coli
The enzyme appears in selected viruses and cellular organisms
Synonyms
3-isopropylmalate dehydrogenase, ipmdh, beta-isopropylmalate dehydrogenase, isopropylmalate dehydrogenase, ipmdh2, ipmdh3, ipmdh1, beta-ipm dehydrogenase, sbipmdh, saci_0600, more
SYNONYM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
NAD-dependent isopropylmalate dehydrogenase
-
two-domain 3-isopropylmalate dehydrogenase
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2-hydroxy-4-methyl-3-carboxyvalerate:NAD+ oxidoreductase
-
-
-
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2R,3S-isopropylmalate:NAD+ oxidoreductase (decaboxylating)
-
-
-
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3-IPM dehydrogenase
-
-
-
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3-IPM-DH
-
-
-
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beta-IPM dehydrogenase
-
-
-
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beta-IPMDH
-
-
-
-
beta-isopropylmalate dehydrogenase
-
-
-
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beta-isopropylmalic enzyme
-
-
-
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dehydrogenase, 3-isopropylmalate
-
-
-
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IPMDH
isopropylmalate dehydrogenase
threo-Ds-3-isopropylmalate dehydrogenase
-
-
-
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
redox reaction
-
-
-
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oxidation
-
-
-
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reduction
-
-
-
-
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
-
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
threo-D-3-isopropylmalate + NAD+
?
show the reaction diagram
domain 1 binds the coenzyme NAD+, while the substrate 3-isopropylmalate binds mainly to domain 2
-
-
?
(2R,3S)-3-isopropylmalate + NAD+
2-oxoisocaproate + NADH + H+ + CO2
show the reaction diagram
-
-
-
-
?
(2R,3S)-3-isopropylmalate + NAD+
4-methyl-2-oxopentanoate + CO2 + NADH + H+
show the reaction diagram
-
-
-
-
ir
3-isopropylmalate + NAD+
?
show the reaction diagram
-
-
-
-
?
D-malate + NAD+
pyruvate + NADH + CO2
show the reaction diagram
-
-
-
-
?
ethylmalate + NAD+
2-oxopentanoate + NADH + H+ + CO2
show the reaction diagram
-
-
-
-
?
isopropylmalate + NAD+
?
show the reaction diagram
-
-
-
-
?
propylmalate + NAD+
?
show the reaction diagram
-
-
-
-
r
tert-butylmalate + NAD+
2-hydroxy-4,4-dimethylpentanoate + NADH + H+ + CO2
show the reaction diagram
-
-
-
-
?
additional information
?
-
NATURAL SUBSTRATE
NATURAL 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+
4-methyl-2-oxopentanoate + CO2 + NADH + H+
show the reaction diagram
-
-
-
-
ir
additional information
?
-
-
the enzyme catalyzes a step in leucine biosynthesis
-
-
?
COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
NAD+
dependent on, cofactor specificity-determining residues, overview
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
K+
-
0.3 mM required for optimal activity
Mg2+
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divalent cation required, saturation is reached at 0.2 mM, activity with Mn2+ is twice as high as with Mg2+
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.011
(2R,3S)-3-isopropylmalate
-
pH 7.5, 37°C
0.301
D-malate
-
pH 7.5, 37°C
0.09
ethylmalate
-
pH 7.6
0.105
isopropylmalate
-
pH 7.6, 40°C
0.321
NAD+
-
pH 7.6, 40°C
0.105
propylmalate
-
pH 7.6
0.214
tert-butylmalate
-
pH 7.6
additional information
additional information
-
thermodynamic and kinetics analysis, overview
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
12
(2R,3S)-3-isopropylmalate
-
pH 7.5, 37°C
0.41
D-malate
-
pH 7.5, 37°C
70
ethylmalate
-
pH 7.6
69
isopropylmalate
-
pH 7.6, 40°C
69
NAD+
-
pH 7.6, 40°C, reaction with isopropylmalate
6
tert-butylmalate
-
pH 7.6
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
1150
(2R,3S)-3-isopropylmalate
-
pH 7.5, 37°C
1.36
D-malate
-
pH 7.5, 37°C
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
-
-
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
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
40 - 80
-
40°C: about 45% of maximal activity, 80°C: about 85% of maximal activity
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
evolution
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for a new phenotypic trait to appear, a genetic mutation is not strictly needed, whereas environmental conditions may play an arbitrary role in enabling or not promiscuous phenotypes. D-malate metabolism is made possible by leucine deprivation, which is a priori unrelated
metabolism
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upon leucine starvation, the physiological concentration of the enzyme raises to a level that is sufficient for metabolizing D-malate thanks to substrate promiscuity. Under these conditions, the enzyme must also play its native role in leucine biosynthesis so the enzyme is phenotypically active in two core metabolic pathways at the same time
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
78780
2 * 78780, sequence calculation
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
homodimer
2 * 78780, sequence calculation
additional information
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
crystal structures of Escherichia coli and Salmonella typhimurium 3-isopropylmalate dehydrogenase and comparison with their thermophilic counterpart from Thermus thermophilus
-
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
D236R/D289K/I290Y/A296V/G337Y
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engineering of the enzyme by site-directed mutagenesis in the cofactor binding pocket to utilize NADP+ as cofactor instead of NAD+, specificity change of factor 20000, modified cofactor binding structure, the mutant shows the same specificity for NADP+ as the wild-type enzyme for NAD+, overview
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
63
-
midpoint of irreversible denaturation
64
-
10 min, 50% inactivation
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
recombinant enzyme
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recombinant enzyme expressed in Escherichia coli
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CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
phylogenetic analysis, comparison to isocitrate dehydrogenase, EC 1.1.1.41, overview
recombinant enzyme expression in Escherichia coli
-
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
induced upon leucine starvation
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RENATURED/Commentary
ORGANISM
UNIPROT
LITERATURE
refolding mechanism of the homodimeric enzyme, dilution of the denatured protein, overview. Association of the two polypeptide chains occurs at the beginning of refolding
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Sekiguchi, T.; Suda, M.; Sekiguchi, T.; Nosoh, Y.
Cloning and DNA homology of 3-isopropylmalate dehydrogenase genes from thermophilic bacilli
FEMS Microbiol. Lett.
36
41-45
1986
[Bacillus] caldolyticus, [Bacillus] caldotenax, Bacillus subtilis, Saccharomyces cerevisiae, Escherichia coli, Thermus thermophilus
-
Manually annotated by BRENDA team
Croft, J.E.; Love, D.R.; Bergquist, P.L.
Expression of leucine genes from an extremely thermophilic bacterium in Escherichia coli
Mol. Gen. Genet.
210
490-497
1987
Escherichia coli, Thermus thermophilus, Salmonella enterica subsp. enterica serovar Typhimurium
Manually annotated by BRENDA team
Wallon, G.; Kryger, G.; Lovett, S.T.; Oshima, T.; Ringe, D.; Petsko, G.A.
Crystal structures of Escherichia coli and Salmonella typhimurium 3-isopropylmalate dehydrogenase and comparison with their thermophilic counterpart from Thermus thermophilus
J. Mol. Biol.
266
1016-1031
1997
Escherichia coli, Salmonella enterica subsp. enterica serovar Typhimurium, Thermus thermophilus
Manually annotated by BRENDA team
Searles, L.L.; Calvo, J.M.
Permeabilized cell and radiochemical assay for beta-isopropylmalate dehydrogenase
Methods Enzymol.
166
225-229
1988
Escherichia coli, Salmonella enterica subsp. enterica serovar Typhimurium
Manually annotated by BRENDA team
Aoshima, M.; Oshima, T.
Stabilization of Escherichia coli isopropylmalate dehydrogenase by single amino acid substitution
Protein Eng.
10
249-254
1997
Escherichia coli, Thermus thermophilus
Manually annotated by BRENDA team
Wallon, G.; Yamamoto, K.; Kirino, H.; Yamagishi, A.; Lovett, S.T.; Petsko, G.A.; Oshima, T.
Purification, catalytic properties and thermostability of 3-isopropylmalate dehydrogenase from Escherichia coli
Biochim. Biophys. Acta
1337
105-112
1997
Escherichia coli, Thermus thermophilus
Manually annotated by BRENDA team
Kalinina, O.V.; Gelfand, M.S.
Amino acid residues that determine functional specificity of NADP- and NAD-dependent isocitrate and isopropylmalate dehydrogenases
Proteins
64
1001-1009
2006
Acidithiobacillus ferrooxidans (Q56268), Agrobacterium tumefaciens (P24404), Arthrospira platensis (Q00412), Aspergillus niger (P87256), Azotobacter vinelandii (P96197), Bacteroides fragilis (P54354), Brassica napus (P29102), Candida maltosa (P07139), Clostridium pasteurianum (P31958), Cyberlindnera jadinii (P08791), Eremothecium gossypii (O60027), Escherichia coli (P30125), Leptospira interrogans (P24015), Mycobacterium tuberculosis variant bovis (P94929), Ogataea angusta (P34733), Saccharomyces cerevisiae (P87267), Salmonella enterica subsp. enterica serovar Typhimurium (P37412), Scheffersomyces stipitis (O94114), Thermus aquaticus (P24098), Thermus thermophilus (P61494), Thermus thermophilus (P61495), Thermus thermophilus HB27 / ATCC BAA-163 / DSM 7039 (P61494), Zymoseptoria tritici (Q9Y897), [Candida] boidinii (Q01987)
Manually annotated by BRENDA team
Lunzer, M.; Miller, S.P.; Felsheim, R.; Dean, A.M.
The biochemical architecture of an ancient adaptive landscape
Science
310
499-501
2005
Escherichia coli
Manually annotated by BRENDA team
Graczer, E.; Varga, A.; Melnik, B.; Semisotnov, G.; Zavodszky, P.; Vas, M.
Symmetrical refolding of protein domains and subunits: example of the dimeric two-domain 3-isopropylmalate dehydrogenases
Biochemistry
48
1123-1134
2009
Vibrio sp., Escherichia coli (P30125), Escherichia coli, Thermus thermophilus (Q5SIY4), Thermus thermophilus, Vibrio sp. I5
Manually annotated by BRENDA team
Hajdu, I.; Szilagyi, A.; Kardos, J.; Zavodszky, P.
A link between hinge-bending domain motions and the temperature dependence of catalysis in 3-isopropylmalate dehydrogenase
Biophys. J.
96
5003-5012
2009
Escherichia coli
Manually annotated by BRENDA team
Khan, M.S.; Gargiulo, S.; Soumillion, P.
Promiscuous activity of 3-isopropylmalate dehydrogenase produced at physiological level affords Escherichia coli growth on D-malate
FEBS Lett.
594
2421-2430
2020
Escherichia coli, Escherichia coli BW25113
Manually annotated by BRENDA team