Information on EC 1.1.1.41 - isocitrate dehydrogenase (NAD+)

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

EC NUMBER
COMMENTARY
1.1.1.41
-
RECOMMENDED NAME
GeneOntology No.
isocitrate dehydrogenase (NAD+)
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
isocitrate + NAD+ = 2-oxoglutarate + CO2 + NADH
show the reaction diagram
-
-
-
-
isocitrate + NAD+ = 2-oxoglutarate + CO2 + NADH
show the reaction diagram
Arg97, and Arg99 contribute to activity, Arg88 is essential for catalysis
-
REACTION TYPE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
oxidation
-
-
-
-
oxidative decarboxylation
-
-
-
-
redox reaction
-
-
-
-
reduction
-
-
-
-
reductive carboxylation
-
-
-
-
PATHWAY
KEGG Link
MetaCyc Link
glutamine biosynthesis III
-
TCA cycle II (plants and fungi)
-
TCA cycle III (animals)
-
Citrate cycle (TCA cycle)
-
Metabolic pathways
-
Biosynthesis of secondary metabolites
-
Microbial metabolism in diverse environments
-
SYSTEMATIC NAME
IUBMB Comments
isocitrate:NAD+ oxidoreductase (decarboxylating)
Requires Mn2+ or Mg2+ for activity. Unlike EC 1.1.1.42, isocitrate dehydrogenase (NADP+), oxalosuccinate cannot be used as a substrate. In eukaryotes, isocitrate dehydrogenase exists in two forms: an NAD+-linked enzyme found only in mitochondria and displaying allosteric properties, and a non-allosteric, NADP+-linked enzyme that is found in both mitochondria and cytoplasm [7]. The enzyme from some species can also use NADP+ but much more slowly [9].
SYNONYMS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
At2g17130
P93032
-
At4g35260
Q8LFC0
-
At4g35650
O81796
-
At5g03290
Q945K7
-
AtIDH I
Q8LFC0
-
AtIDH II
P93032
-
AtIDH V
Q945K7
-
AtIDH VI
Q8LG77
-
beta-decarboxylating dehydrogenase
-
-
beta-ketoglutaric-isocitric carboxylase
-
-
-
-
ICDH
Acidithiobacillus thiooxidans ON107
Q8GAX0
-
-
IDH
Arabidopsis thaliana Landsberg
-
-
-
IDH
G1APK2, G1APK3
-
IDH
Rhodosporidium toruloides AS 2.1389
G1APK2, G1APK3
-
-
IDH
Saccharomyces cerevisiae MMY011
-
-
-
IDH
-
-
IDH
Zymomonas mobilis ATCC10988
-
-
-
IDH III
-, O81796
-
IDH-I
Q8LFC0
-
IDH-II
P93032
-
IDH-V
Q945K7
-
IDH1
-
-
-
-
IDH1
-
-
IDH1
Saccharomyces cerevisiae MMY011
-
-
-
IDH2
Saccharomyces cerevisiae MMY011
-
-
-
IDHa
Saccharomyces cerevisiae MMY011
-
-
-
isocitrate dehydrogenase
-
-
isocitrate dehydrogenase
-
-
isocitrate dehydrogenase
-
-
isocitrate dehydrogenase
-
-
isocitrate dehydrogenase
-
-
isocitrate dehydrogenase 2
-
-
isocitrate-homoisocitrate dehydrogenase
-
-
isocitric acid dehydrogenase
-
-
-
-
isocitric dehydrogenase
-
-
-
-
mitochondrial NAD-dependent isocitrate dehydrogenase
-
-
NAD dependent isocitrate dehydrogenase
-
-
-
-
NAD isocitrate dehydrogenase
-
-
-
-
NAD isocitric dehydrogenase
-
-
-
-
NAD(P)+-dependent isocitrate dehydrogenase
-
-
NAD+-dependent ICDH
-
-
NAD+-dependent isocitrate dehydrogenase
-
-
NAD+-dependent isocitrate dehydrogenase
Q8GAX0
-
NAD+-dependent isocitrate dehydrogenase
Acidithiobacillus thiooxidans ON107
Q8GAX0
-
-
NAD+-dependent isocitrate dehydrogenase
-
-
NAD+-dependent isocitrate dehydrogenase
Arabidopsis thaliana Landsberg
-
-
-
NAD+-dependent isocitrate dehydrogenase
G1APK2, G1APK3
-
NAD+-dependent isocitrate dehydrogenase
Rhodosporidium toruloides AS 2.1389
G1APK2, G1APK3
-
-
NAD+-dependent isocitrate dehydrogenase
-
-
NAD+-dependent isocitrate dehydrogenase 1
-
-
NAD+-specific ICDH
-
-
-
-
NAD+-specific IDH
G1APK2, G1APK3
-
NAD+-specific IDH
Rhodosporidium toruloides AS 2.1389
G1APK2, G1APK3
-
-
NAD+-specific IDH
-
-
NAD+-specific isocitrate dehydrogenase
-
-
NAD+-specific isocitrate dehydrogenase
P28241, P28834
-
NAD+-specific isocitrate dehydrogenase
Saccharomyces cerevisiae MMY011
-
-
-
NAD-Dependent IDH
-
-
NAD-dependent isocitrate dehydrogenase
-, O81796
-
NAD-dependent isocitrate dehydrogenase
P93032, Q8LFC0
-
NAD-dependent isocitrate dehydrogenase
Q8LG77
-
NAD-dependent isocitrate dehydrogenase
Q945K7
-
NAD-dependent isocitrate dehydrogenase
-
-
NAD-dependent isocitrate dehydrogenase
-
-
NAD-dependent isocitrate dehydrogenase
-
-
NAD-dependent isocitrate dehydrogenase
-
-
NAD-ICDH
-
-
NAD-isocitrate dehydrogenase
-
-
NAD-isocitrate dehydrogenase
-
-
NAD-linked isocitrate dehydrogenase
-
-
-
-
NAD-specific isocitrate dehydrogenase
-
-
-
-
NAD-specific isocitrate dehydrogenase
-
-
PF0202
Q8U488
gene name
threo-DS-isocitrate:NAD+ oxidoreductase (decarboxylating)
-
-
CAS REGISTRY NUMBER
COMMENTARY
9001-58-5
-
ORGANISM
COMMENTARY
LITERATURE
SEQUENCE CODE
SEQUENCE DB
SOURCE
Acidithiobacillus thiooxidans ON107
strain ON107
SwissProt
Manually annotated by BRENDA team
isocitrate dehydrogenase (NAD) catalytic subunit 5, mitochondrial (precursor)
SwissProt
Manually annotated by BRENDA team
isocitrate dehydrogenase (NAD) catalytic subunit 6, mitochondrial (precursor)
SwissProt
Manually annotated by BRENDA team
isocitrate dehydrogenase (NAD) regulatory subunit 1, mitochondrial (precursor)
SwissProt
Manually annotated by BRENDA team
isocitrate dehydrogenase (NAD) regulatory subunit 2, mitochondrial (precursor)
SwissProt
Manually annotated by BRENDA team
isocitrate dehydrogenase (NAD) regulatory subunit 3, mitochondrial (precursor)
SwissProt
Manually annotated by BRENDA team
Arabidopsis thaliana Landsberg
Landsberg
-
-
Manually annotated by BRENDA team
pigeon
-
-
Manually annotated by BRENDA team
cv. 294 040 Mrgrt Kelvedon Wonder
-
-
Manually annotated by BRENDA team
Pseudomonas sp. W 6
W 6
-
-
Manually annotated by BRENDA team
gene RtIDH1; gene RtIDH1
UniProt
Manually annotated by BRENDA team
gene RtIDH2; gene RtIDH2
UniProt
Manually annotated by BRENDA team
Rhodosporidium toruloides AS 2.1389
gene RtIDH1; gene RtIDH1
UniProt
Manually annotated by BRENDA team
Rhodosporidium toruloides AS 2.1389
gene RtIDH2; gene RtIDH2
UniProt
Manually annotated by BRENDA team
Saccharomyces cerevisiae MMY011
strain MMY011
-
-
Manually annotated by BRENDA team
Sarcophaga barbata
-
-
-
Manually annotated by BRENDA team
gene SlIDH1
-
-
Manually annotated by BRENDA team
waterbug
-
-
-
Manually annotated by BRENDA team
citrate-overproducing yeast, strain BKM Y-2373
-
-
Manually annotated by BRENDA team
ssp. mobiliss
-
-
Manually annotated by BRENDA team
Zymomonas mobilis ATCC10988
ssp. mobiliss
-
-
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
evolution
-
efficacy of association mapping for dissecting natural variation in primary metabolic pathways, the considerable genetic diversity observed in maize CCM genes underlies heritable phenotypic variation in enzyme activities and can be useful to identify putative functional sites
evolution
-
the recombinant ZmIDH is mainly NAD+-dependent and its catalytic efficiency (kcat/Km) is relative low when compared to the prokaryotic NADP+-IDHs
evolution
-
the ancient NAD-dependent IDHs might be the underlying origin of phosphorylation mechanism used by their bacterial NADP-dependent homologues
evolution
Zymomonas mobilis ATCC10988
-
the recombinant ZmIDH is mainly NAD+-dependent and its catalytic efficiency (kcat/Km) is relative low when compared to the prokaryotic NADP+-IDHs
-
metabolism
G1APK2, G1APK3, -
regulatory controls of key enzymes during microbial lipid accumulation involving the enzyme, overview; regulatory controls of key enzymes during microbial lipid accumulation involving the enzyme, overview
metabolism
-
yeast IDH is regulated both by allostery and by covalent formation of a disulfide bond, and these regulatory mechanisms contribute to modulation of respiratory metabolism in vivo
metabolism
Rhodosporidium toruloides AS 2.1389
-
regulatory controls of key enzymes during microbial lipid accumulation involving the enzyme, overview; regulatory controls of key enzymes during microbial lipid accumulation involving the enzyme, overview
-
additional information
-
reduction of mitochondrial IDH activity has little effect on the relative electron transport or assimilation rates and a minor reduction in the maximum efficiency of PSII
additional information
-
interactions between sulfhydryl side chains of IDH2 Cys150 residues limit access to eight D-isocitrate and four AMP binding sites. In the presence of dithiothreitol, all ligand binding sites except for two potential NAD+ sites can be occupied; the IDH2 Cys-150 residue controls access to isocitrate binding sites. The wild-type enzyme displays four binding sites for isocitrate and two binding sites for AMP in the absence of dithiothreitol, and these numbers increase to eight and four in the presence of dithiothreitol, respectively
additional information
-
Ser102 plays an important role in substrate binding and is required for the enzyme function
SUBSTRATE
PRODUCT                      
REACTION DIAGRAM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
8-(4-bromo-2,3-dioxobutylthio)-NAD+ + isocitrate
2-oxoglutarate + CO2 + 8-(4-bromo-2,3-dioxobutylthio)-NADH
show the reaction diagram
-
-
-
-
?
D-homoisocitrate + NAD+
? + NADH
show the reaction diagram
-
-
-
-
?
D-isocitrate + NAD+
2-oxoglutarate + CO2 + NADH
show the reaction diagram
-
-
-
-
?
D-isocitrate + NAD+
2-oxoglutarate + CO2 + NADH
show the reaction diagram
-
-
-
-
?
D-isocitrate + NAD+
2-oxoglutarate + CO2 + NADH
show the reaction diagram
-
-
-
-
?
D-isocitrate + NAD+
2-oxoglutarate + CO2 + NADH
show the reaction diagram
P28241, P28834, -
-
-
-
ir
D-isocitrate + NAD+
2-oxoglutarate + CO2 + NADH
show the reaction diagram
-
-
-
-
ir
D-isocitrate + NAD+
2-oxoglutarate + CO2 + NADH
show the reaction diagram
-, O81796, P93032, Q8LFC0, Q8LG77, Q945K7
-
-
-
?
D-isocitrate + NAD+
2-oxoglutarate + CO2 + NADH
show the reaction diagram
-
-
-
-
?
D-isocitrate + NAD+
2-oxoglutarate + CO2 + NADH
show the reaction diagram
-
-
-
-
?
D-isocitrate + NAD+
2-oxoglutarate + CO2 + NADH
show the reaction diagram
-
-
-
-
r
D-isocitrate + NAD+
2-oxoglutarate + CO2 + NADH
show the reaction diagram
-
-
-
-
?
D-isocitrate + NAD+
2-oxoglutarate + CO2 + NADH
show the reaction diagram
-
-
-
-
?
D-isocitrate + NAD+
2-oxoglutarate + CO2 + NADH
show the reaction diagram
-
-
-
-
r
D-isocitrate + NAD+
2-oxoglutarate + CO2 + NADH
show the reaction diagram
-
catalytic residues binding isocitrate are located on subunit IDH2, while regulatory residues binding isocitrate are located on subunit IDH1
-
-
?
D-isocitrate + NAD+
2-oxoglutarate + CO2 + NADH
show the reaction diagram
Saccharomyces cerevisiae MMY011
-
-
-
-
ir
D-isocitrate + NAD+
2-oxoglutarate + CO2 + NADH
show the reaction diagram
Saccharomyces cerevisiae MMY011
-
-
-
-
?
DL-isocitrate + NAD+
2-oxoglutarate + CO2 + NADH
show the reaction diagram
O43837
-
-
-
?
DL-isocitrate + NAD+
2-oxoglutarate + CO2 + NADH
show the reaction diagram
-
-
-
-
?
DL-isocitrate + NAD+
2-oxoglutarate + CO2 + NADH
show the reaction diagram
-
-
-
-
r
DL-isocitrate + NAD+
2-oxoglutarate + CO2 + NADH
show the reaction diagram
-
isocitrate binds at 2 functionally distinct sites
-
-
?
isocitrate + NAD+
2-oxoglutarate + CO2 + NADH
show the reaction diagram
-
-
-
-
?
isocitrate + NAD+
2-oxoglutarate + CO2 + NADH
show the reaction diagram
-
-
-
-
?
isocitrate + NAD+
2-oxoglutarate + CO2 + NADH
show the reaction diagram
-
-
-
-
?
isocitrate + NAD+
2-oxoglutarate + CO2 + NADH
show the reaction diagram
-
-
-
-
?
isocitrate + NAD+
2-oxoglutarate + CO2 + NADH
show the reaction diagram
-
-
-
-
?
isocitrate + NAD+
2-oxoglutarate + CO2 + NADH
show the reaction diagram
-
-
-
-
?
isocitrate + NAD+
2-oxoglutarate + CO2 + NADH
show the reaction diagram
-
-
-
-
?
isocitrate + NAD+
2-oxoglutarate + CO2 + NADH
show the reaction diagram
-
-
-
-
?
isocitrate + NAD+
2-oxoglutarate + CO2 + NADH
show the reaction diagram
-
-
-
-
?
isocitrate + NAD+
2-oxoglutarate + CO2 + NADH
show the reaction diagram
-
-
-
-
?
isocitrate + NAD+
2-oxoglutarate + CO2 + NADH
show the reaction diagram
-
-
-
-
?
isocitrate + NAD+
2-oxoglutarate + CO2 + NADH
show the reaction diagram
-
-
-
-
?
isocitrate + NAD+
2-oxoglutarate + CO2 + NADH
show the reaction diagram
-
-
-
-
?
isocitrate + NAD+
2-oxoglutarate + CO2 + NADH
show the reaction diagram
-
-
-
-
?
isocitrate + NAD+
2-oxoglutarate + CO2 + NADH
show the reaction diagram
-
-
-
-
?
isocitrate + NAD+
2-oxoglutarate + CO2 + NADH
show the reaction diagram
-
-
-
-
?
isocitrate + NAD+
2-oxoglutarate + CO2 + NADH
show the reaction diagram
-
-
-
-
?
isocitrate + NAD+
2-oxoglutarate + CO2 + NADH
show the reaction diagram
-
-
-
-
?
isocitrate + NAD+
2-oxoglutarate + CO2 + NADH
show the reaction diagram
-
-
-
-
?
isocitrate + NAD+
2-oxoglutarate + CO2 + NADH
show the reaction diagram
-
-
-
-
?
isocitrate + NAD+
2-oxoglutarate + CO2 + NADH
show the reaction diagram
-
-
-
-
?
isocitrate + NAD+
2-oxoglutarate + CO2 + NADH
show the reaction diagram
-
-
-
-
?
isocitrate + NAD+
2-oxoglutarate + CO2 + NADH
show the reaction diagram
-
-
-
-
?
isocitrate + NAD+
2-oxoglutarate + CO2 + NADH
show the reaction diagram
-, Q8GAX0
-
-
-
?
isocitrate + NAD+
2-oxoglutarate + CO2 + NADH
show the reaction diagram
G1APK2, G1APK3, -
-
-
-
?
isocitrate + NAD+
2-oxoglutarate + CO2 + NADH
show the reaction diagram
-
enzyme has a regulatory role in the tricarboxylic cycle
-
-
?
isocitrate + NAD+
2-oxoglutarate + CO2 + NADH
show the reaction diagram
-
enzyme performs the rate-limiting step in the mitochondrial tricarboxylic cycle and is subject to complex allosteric regulation
-
-
?
isocitrate + NAD+
2-oxoglutarate + CO2 + NADH
show the reaction diagram
-
key enzyme in the Krebs cycle
-
-
?
isocitrate + NAD+
2-oxoglutarate + CO2 + NADH
show the reaction diagram
-
pyridine nucleotide contents in mitochondria and cytosol, regulation, overview
-
-
ir
isocitrate + NAD+
2-oxoglutarate + CO2 + NADH
show the reaction diagram
-
subunit IDH-I can substitute for a deficient mutant subunit IDH-II
-
-
?
isocitrate + NAD+
2-oxoglutarate + CO2 + NADH
show the reaction diagram
-
poor performance of the recombinant ZmIDH in decarboxylation
-
-
?
isocitrate + NAD+
2-oxoglutarate + CO2 + NADH
show the reaction diagram
-, Q8U488
wild-type enzyme is specific for NAD+, low activity with NADP+ as cofactor, mutant D328K shows dual coenzyme specificity, cofactor preference of mutant D328K/I329Y is shifted from NAD+ to NADP+
-
-
?
isocitrate + NAD+
2-oxoglutarate + CO2 + NADH
show the reaction diagram
Rhodosporidium toruloides AS 2.1389
G1APK2, G1APK3
-
-
-
?
isocitrate + NAD+
2-oxoglutarate + CO2 + NADH
show the reaction diagram
Acidithiobacillus thiooxidans ON107
Q8GAX0
-
-
-
?
isocitrate + NAD+
2-oxoglutarate + CO2 + NADH
show the reaction diagram
Arabidopsis thaliana Landsberg
-
key enzyme in the Krebs cycle, subunit IDH-I can substitute for a deficient mutant subunit IDH-II
-
-
?
isocitrate + NAD+
2-oxoglutarate + CO2 + NADH
show the reaction diagram
Pseudomonas sp. W 6
-
-
-
-
?
isocitrate + NAD+
2-oxoglutarate + CO2 + NADH
show the reaction diagram
Zymomonas mobilis ATCC10988
-
-, poor performance of the recombinant ZmIDH in decarboxylation
-
-
?
isocitrate + NAD+
2-oxoglutarate + CO2 + NADH + H+
show the reaction diagram
-
-
-
-
?
isocitrate + NAD+
2-oxoglutarate + CO2 + NADH + H+
show the reaction diagram
P28241, P28834, -
-
-
-
?
isocitrate + NAD+
2-oxoglutarate + CO2 + NADH + H+
show the reaction diagram
-
the enzyme is NAD+-dependent
-
-
?
isocitrate + NAD+
2-oxoglutarate + CO2 + NADH + H+
show the reaction diagram
-
low activity with NADP+. Km-value for NADP+ is about 65fold higher than the KM-value for NAD+
-
-
?
isocitrate + NAD+
2-oxoglutarate + NADH + H+ + CO2
show the reaction diagram
-
-
-
-
?
isocitrate + NAD+
2-oxoglutarate + NADH + H+ + CO2
show the reaction diagram
-
-
-
-
?
isocitrate + NAD+
2-oxoglutarate + NADH + H+ + CO2
show the reaction diagram
-
-
-
-
?
isocitrate + NAD+
2-oxoglutarate + NADH + H+ + CO2
show the reaction diagram
-
IDH1 is an enzyme that catalyzes the oxidative decarboxylation of isocitrate into alpha-ketoglutarate utilizing either NAD+ or NADP+ as cosubstrates
-
-
?
isocitrate + NAD+
2-oxoglutarate + NADH + H+ + CO2
show the reaction diagram
-
residue Y137 of subunit beta is involved in NAD+ binding and allosteric activation by ADP, residue Y126 of subunit alpha is required for catalytic activity and likely acts as a general acid in the reaction, gammaY135 is also required for catalytic activity and may be involved in proper folding of the enzyme. The corresponding tyrosines in the three dissimilar subunits of NAD-IDH thus have distinctive functions
-
-
?
isocitrate + NADP+
2-oxoglutarate + CO2 + NADPH
show the reaction diagram
-
poor performance of the recombinant ZmIDH in decarboxylation
-
-
?
isocitrate + NADP+
2-oxoglutarate + CO2 + NADPH
show the reaction diagram
-, Q8U488
wild-type enzyme is specific for NAD+, low activity with NADP+ as cofactor, mutant D328K shows dual coenzyme specificity, cofactor preference of mutant D328K/I329Y is shifted from NAD+ to NADP+
-
-
?
threo-DS-isocitrate + NAD+
2-oxoglutarate + CO2 + NADH
show the reaction diagram
-
-
-
-
?
threo-DS-isocitrate + NAD+
2-oxoglutarate + CO2 + NADH
show the reaction diagram
-
-
-
-
ir
isocitrate + NADP+
2-oxoglutarate + CO2 + NADPH
show the reaction diagram
Zymomonas mobilis ATCC10988
-
poor performance of the recombinant ZmIDH in decarboxylation
-
-
?
additional information
?
-
-
allosteric regulation, enzyme specifically binds to 5'-untranslated regions of yeast mitochondrial mRNAs, and transcripts containing these regions allosterically inhibit the enzyme, which can be relieved by activator AMP in presence of isocitrate, complex formation, overview
-
-
-
additional information
?
-
-
enzyme is involved in tricarboxylic acid cycle and plays a key role in the regulation of biosynthesis of citrate and isocitrate, yeast is overproducing citrate under nitrogen deficiency in presence of glucose
-
-
-
additional information
?
-
-
isocitrate dehydrogenase is an essential enzyme for riboflavin production in Ashbya gossypii
-
-
-
additional information
?
-
-
the enzyme is also active with NADP+ and NADPH, cf. EC 1.1.1.42
-
-
-
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
D-isocitrate + NAD+
2-oxoglutarate + CO2 + NADH
show the reaction diagram
-
-
-
-
?
DL-isocitrate + NAD+
2-oxoglutarate + CO2 + NADH
show the reaction diagram
-
-
-
-
?
DL-isocitrate + NAD+
2-oxoglutarate + CO2 + NADH
show the reaction diagram
-
-
-
-
r
isocitrate + NAD+
2-oxoglutarate + CO2 + NADH
show the reaction diagram
-
-
-
-
?
isocitrate + NAD+
2-oxoglutarate + CO2 + NADH
show the reaction diagram
-
-
-
-
?
isocitrate + NAD+
2-oxoglutarate + CO2 + NADH
show the reaction diagram
-
-
-
-
?
isocitrate + NAD+
2-oxoglutarate + CO2 + NADH
show the reaction diagram
-
-
-
-
?
isocitrate + NAD+
2-oxoglutarate + CO2 + NADH
show the reaction diagram
-
-
-
-
?
isocitrate + NAD+
2-oxoglutarate + CO2 + NADH
show the reaction diagram
-
-
-
-
?
isocitrate + NAD+
2-oxoglutarate + CO2 + NADH
show the reaction diagram
-
-
-
-
?
isocitrate + NAD+
2-oxoglutarate + CO2 + NADH
show the reaction diagram
-
-
-
-
?
isocitrate + NAD+
2-oxoglutarate + CO2 + NADH
show the reaction diagram
-
-
-
-
?
isocitrate + NAD+
2-oxoglutarate + CO2 + NADH
show the reaction diagram
-
-
-
-
?
isocitrate + NAD+
2-oxoglutarate + CO2 + NADH
show the reaction diagram
-
-
-
-
?
isocitrate + NAD+
2-oxoglutarate + CO2 + NADH
show the reaction diagram
-
-
-
-
?
isocitrate + NAD+
2-oxoglutarate + CO2 + NADH
show the reaction diagram
-
-
-
-
?
isocitrate + NAD+
2-oxoglutarate + CO2 + NADH
show the reaction diagram
-
-
-
-
?
isocitrate + NAD+
2-oxoglutarate + CO2 + NADH
show the reaction diagram
-
-
-
-
?
isocitrate + NAD+
2-oxoglutarate + CO2 + NADH
show the reaction diagram
-
-
-
-
?
isocitrate + NAD+
2-oxoglutarate + CO2 + NADH
show the reaction diagram
-
-
-
-
?
isocitrate + NAD+
2-oxoglutarate + CO2 + NADH
show the reaction diagram
-
-
-
-
?
isocitrate + NAD+
2-oxoglutarate + CO2 + NADH
show the reaction diagram
-
-
-
-
?
isocitrate + NAD+
2-oxoglutarate + CO2 + NADH
show the reaction diagram
-
-
-
-
?
isocitrate + NAD+
2-oxoglutarate + CO2 + NADH
show the reaction diagram
-
-
-
-
?
isocitrate + NAD+
2-oxoglutarate + CO2 + NADH
show the reaction diagram
-
-
-
-
?
isocitrate + NAD+
2-oxoglutarate + CO2 + NADH
show the reaction diagram
-
-
-
-
?
isocitrate + NAD+
2-oxoglutarate + CO2 + NADH
show the reaction diagram
-, Q8GAX0
-
-
-
?
isocitrate + NAD+
2-oxoglutarate + CO2 + NADH
show the reaction diagram
G1APK2, G1APK3, -
-
-
-
?
isocitrate + NAD+
2-oxoglutarate + CO2 + NADH
show the reaction diagram
-
enzyme has a regulatory role in the tricarboxylic cycle
-
-
?
isocitrate + NAD+
2-oxoglutarate + CO2 + NADH
show the reaction diagram
-
enzyme performs the rate-limiting step in the mitochondrial tricarboxylic cycle and is subject to complex allosteric regulation
-
-
?
isocitrate + NAD+
2-oxoglutarate + CO2 + NADH
show the reaction diagram
-
key enzyme in the Krebs cycle
-
-
?
isocitrate + NAD+
2-oxoglutarate + CO2 + NADH
show the reaction diagram
-
pyridine nucleotide contents in mitochondria and cytosol, regulation, overview
-
-
ir
isocitrate + NAD+
2-oxoglutarate + NADH + H+ + CO2
show the reaction diagram
-
-
-
-
?
isocitrate + NAD+
2-oxoglutarate + NADH + H+ + CO2
show the reaction diagram
-
-
-
-
?
isocitrate + NAD+
2-oxoglutarate + NADH + H+ + CO2
show the reaction diagram
-
-
-
-
?
isocitrate + NAD+
2-oxoglutarate + NADH + H+ + CO2
show the reaction diagram
-
IDH1 is an enzyme that catalyzes the oxidative decarboxylation of isocitrate into alpha-ketoglutarate utilizing either NAD+ or NADP+ as cosubstrates
-
-
?
isocitrate + NAD+
2-oxoglutarate + CO2 + NADH
show the reaction diagram
Rhodosporidium toruloides AS 2.1389
G1APK2, G1APK3
-
-
-
?
isocitrate + NAD+
2-oxoglutarate + CO2 + NADH
show the reaction diagram
Acidithiobacillus thiooxidans ON107
Q8GAX0
-
-
-
?
isocitrate + NAD+
2-oxoglutarate + CO2 + NADH
show the reaction diagram
Arabidopsis thaliana Landsberg
-
key enzyme in the Krebs cycle
-
-
?
isocitrate + NAD+
2-oxoglutarate + CO2 + NADH
show the reaction diagram
Pseudomonas sp. W 6
-
-
-
-
?
threo-DS-isocitrate + NAD+
2-oxoglutarate + CO2 + NADH
show the reaction diagram
-
-
-
-
?
isocitrate + NAD+
2-oxoglutarate + CO2 + NADH
show the reaction diagram
Zymomonas mobilis ATCC10988
-
-
-
-
?
additional information
?
-
-
allosteric regulation, enzyme specifically binds to 5'-untranslated regions of yeast mitochondrial mRNAs, and transcripts containing these regions allosterically inhibit the enzyme, which can be relieved by activator AMP in presence of isocitrate, complex formation, overview
-
-
-
additional information
?
-
-
enzyme is involved in tricarboxylic acid cycle and plays a key role in the regulation of biosynthesis of citrate and isocitrate, yeast is overproducing citrate under nitrogen deficiency in presence of glucose
-
-
-
additional information
?
-
-
isocitrate dehydrogenase is an essential enzyme for riboflavin production in Ashbya gossypii
-
-
-
COFACTOR
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
NAD+
-
specific for
NAD+
-
specific for
NAD+
-, Q8GAX0
highly preferred cofactor, 78fold higher activity than with NADP+
NAD+
-
specific for, binding site at subunit IDH2
NAD+
-
specific for
NAD+
-
dependent on
NAD+
-, O81796, P93032, Q8LFC0, Q8LG77, Q945K7
-
NAD+
-
specific for NAD+
NAD+
G1APK2, G1APK3, -
dependent on; dependent on
NAD+
-
wild-type enzyme is specific for NAD+, low activity with NADP+ as cofactor, mutant D328K shows dual coenzyme specificity, cofactor preference of mutant D328K/I329Y is shifted from NAD+ to NADP+
NAD+
-
dependent on, one NAD+ site per enzyme tetramer, two functional NAD+ binding sites in the wild-type enzyme; two NAD+ binding sites located on subunit IDH2
NAD+
-
ZmIDH displays a 165fold (kcat/Km) preference for NAD+ over NADP+ with Mg2+, and 142fold with Mn2+
NADP+
-, Q8GAX0
78fold lower activity than with NAD+
NADP+
-
wild-type enzyme is specific for NAD+, low activity with NADP+ as cofactor, mutant D328K shows dual coenzyme specificity, cofactor preference of mutant D328K/I329Y is shifted from NAD+ to NADP+
NADP+
-
ZmIDH displays a 165fold (kcat/Km) preference for NAD+ over NADP+ with Mg2+, and 142fold with Mn2+
additional information
-
the enzyme is also active with NADP+ and NADPH, cf. EC 1.1.1.42
-
METALS and IONS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
Ca2+
-
less effective than Mn2+ or Mg2+
Ca2+
-
-
Co2+
-
less effective than Mg2+ or Mn2+
Co2+
-
less effective than Mg2+ or Mn2+
Co2+
-
essential divalent metal ion
Co2+
-
activates, 42.5% activity compared to Mn2+
Mg2+
-
required, active substrate is Mg-DL-isocitrate chelate
Mg2+
-
free form inhibits; required, active substrate is Mg-DL-isocitrate chelate
Mg2+
-
-
Mg2+
-
required, active substrate is Mg-DL-isocitrate chelate
Mg2+
-
binding site at subunit IDH2, active site
Mg2+
-
essential divalent metal ion
Mg2+
-
required, activates
Mg2+
-
activates, 78% activity compared to Mn2+
Mn2+
-
requires divalent cations
Mn2+
-
requires divalent cations
Mn2+
-
requires divalent cations
Mn2+
-
-
Mn2+
-
requires divalent cations
Mn2+
-
-
Mn2+
-
alpha subunit Asp230 and gamma-subunit Asp215 may interact directly with the Mn2+. KM-value: 0.22 mM for wild-type enzyme, 0.32 mM for alpha-subunit mutant enzyme D206N, 7.13 mM for alpha-subunit mutant enzyme D230C, 0.46 mM for alpha-subunit mutant enzyme D234C, 0.1 mM for beta-subunit mutant enzyme D217N, 21.1 mM for gamma-subunit mutant enzyme D215N; essential divalent metal ion
Mn2+
-
required. KM-value: 0.067 mM for wild-type enzyme, 1.09 mM for the alpha-subunit mutant D181N, 0.14 mM for the beta-subunit mutant D192N. 4.8 mM for the gamma-subunit mutant D190N
Mn2+
-
activates, Km values for wild-type and betaY137 mutants are 0.11-0.18 mM
Mn2+
-
activates, best cation
Zn2+
-
less effective than Mn2+ or Mg2+
Mn2+
-
best divalent cation
additional information
-
the recombinant ZmIDH activity is completely dependent on the divalent cation and Mn2+ is the most effective cation
additional information
-
the enzyme is dependent on divalent cations
INHIBITORS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
130-nucleotide transcript containing the 5'-untranslated regions of the yeast mitochondrial COX2 mRNA
-
inhibition with a 50% reduction in activity observed with 40 nM mRNA
-
2-hydroxyethylamine-N,N-diacetate
-
-
2-oxoglutarate
-
-
2-Oxopropane-1,1,3-tricarboxylate
-
only in presence of ADP
beta-mercapto-alpha-ketoglutarate
-
inhibition in presence and absence of AMP, competitive inhibition
Bilirubin
-
-
Chicago sky blue
-
-
citrate
-
with constant concentrations of isocitrate, NAD+ and Mg2+ up to 10 mM and without AMP, citrate is an activator
Congo red
-
-
Cu2+
-
complete inhibition
D,L-hibiscusate
-
with constant concentrations of isocitrate, NAD+ and Mg2+ up to 10 mM and without AMP, D,L-hibiscusate is an activator
D,L-threo-alpha-methylisocitrate
-
inhibition in presence and absence of AMP, competitive inhibition
D-malate
-
inhibition only in absence of AMP
D-Tartrate
-
inhibition only in absence of AMP
Diamide
-
treatment of the affinity-purified enzyme with diamide results in the formation of disulfide bonds and in decreased activity for the wild type enzyme, the effect is reversible by the addition of dithiothreitol
Diamide
-
; increases disulfide content of the enzyme
fluorescein
-
halogenated derivatives
Fluorocitrate
-
with constant concentrations of isocitrate, NAD+ and Mg2+ up to 10 mM and without AMP, fluorocitrate is an activator
fumarate
-
inhibition only in absence of AMP
gamma-aminobutyric acid
-
slight inhibition
glutamate
-
slight inhibition
glyoxylate
-
with oxaloacetate, concomitantly added
glyoxylate
-
slight inhibition
homocitrate
-
inhibition only in absence of AMP
L-garciniate
-
inhibition in presence and absence of AMP
-
L-hibiscusate
-
with constant concentrations of isocitrate, NAD+ and Mg2+ up to 10 mM and without AMP, L-hibiscusate is an activator
-
L-Malate
-
inhibition only in absence of AMP, competitive inhibition
L-Tartrate
-
inhibition only in absence of AMP
Maleate
-
inhibition only in absence of AMP
malonate
-
inhibition only in absence of AMP
Mg2+
-
free form
mitochondrial COX2 UTR RNA
-
-
-
mRNA
-
enzyme specifically binds to 5'-untranslated regions of yeast mitochondrial mRNAs, and transcripts containing these regions allosterically inhibit the enzyme, which can be relieved by activator AMP in presence of isocitrate, complex formation, overview
NADH
-
competitive inhibitor
NADH
-
competitive inhibitor
NADH
-
inhibits ICDH-2
NADH
-
complete inhibition at 0.2 mM, competitive
NADH
-
competitive
NADPH
-
noncompetitive inhibitor
NADPH
-
noncompetitive
Nitrilotriacetate
-
-
oxaloacetate
-
slight inhibition
p-hydroxymercuribenzoate
-
-
pyruvate
-
with oxaloacetate, concomitantly added, less effective than glyoxylate + oxaloacetate
succinate
-
inhibition only in absence of AMP
succinate
-
slight inhibition
Succinic semialdehyde
-
slight inhibition
Sulfobromophthalein
-
-
Thiocyanate
-
-
Zn2+
-
complete inhibition
additional information
-
the enzyme is not affected by NADP+, HCO3-, and 2-oxoglutarate
-
additional information
-
enzyme is not affected by gamma-aminobutyric acid and glutamate
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
ADP
-
allosteric regulation, determination of mol ADP bound to an enzyme tetramer of wild-type and mutant enzymes at different starting concentrations, overview
ADP
-
activates. Michaelis-Menten constant for DL-isocitrate is lowered 3.5-fold in the wild-type IDH. The substitution of asparagine for aspartate in alpha-mutant enzyme D181N, beta-subunit mutant enzyme D192N, and gamma-subunit mutant enzyme D190N abolishes this allosteric effect of ADP on Km
ADP
-
allosteric activation by ADP involving residue betaY126. In the presence of 1 mM ADP, the Km,isocitrate is reduced almost equally in the wild-type, 3.6fold, and the alphaY126E mutant, 4.3fold
AMP
-
activates ICDH-1
AMP
-
activation of the enzyme and reduction of enzyme inhibition by mitochondrial mRNA, highly enhanced by presence of isocitrate, complex formation, overview
AMP
-
allosteric activation
AMP
-
allosteric activator, binding site at subunit IDH1
AMP
-
allosteric activation, binds to subunit IDH1
AMP
-
allosteric activation, isocitrate binding is essential for binding of AMP to IDH1 subunits; four AMP binding sites located on subunit IDH2
DTT
-
; decreases disulfide content of the enzyme, kinetics of enzyme mutants in presence or absence of DTT, overview
additional information
-
the enzyme is not affected by NADP+, HCO3-, and 2-oxoglutarate
-
additional information
-
enzyme is not affected by gamma-aminobutyric acid
-
KM VALUE [mM]
KM VALUE [mM] Maximum
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.03
-
D,L-isocitrate
-
-
0.11
-
D,L-isocitrate
-
-
0.45
-
D,L-isocitrate
-
-
0.09
-
D-isocitrate
-
octameric wild-type enzyme with AMP, without DTT, pH 7.4, 24C
0.1
-
D-isocitrate
-
octameric enzyme mutant IDH1/IDH2C150S with AMP, with or without DTT, pH 7.4, 24C; octameric wild-type enzyme with AMP and DTT, pH 7.4, 24C
0.17
-
D-isocitrate
-
octameric enzyme mutant IDH1/IDH2C56S/C150S/C242S with AMP, without DTT, pH 7.4, 24C
0.19
-
D-isocitrate
-
octameric enzyme mutant IDH1/IDH2C56S/C150S/C242S with AMP and DTT, pH 7.4, 24C
0.2
-
D-isocitrate
-
octameric enzyme mutant IDH1/IDH2C56S/C242S with AMP and DTT, pH 7.4, 24C
0.32
-
D-isocitrate
-
octameric enzyme mutant IDH1/IDH2C56S/C242S with AMP, without DTT, pH 7.4, 24C
0.48
-
D-isocitrate
-
octameric enzyme IDH1G15D/IDH2 with AMP and DTT, pH 7.4, 24C
0.5
-
D-isocitrate
-
octameric enzyme IDH1G15D/IDH2 with AMP, without DTT, pH 7.4, 24C
0.51
-
D-isocitrate
-
octameric wild-type enzyme without AMP, with DTT, pH 7.4, 24C
0.53
-
D-isocitrate
-
octameric enzyme mutant IDH1/IDH2C150S without AMP and DTT, pH 7.4, 24C
0.54
-
D-isocitrate
-
octameric enzyme mutant IDH1/IDH2C150S without AMP, with DTT, pH 7.4, 24C
0.56
-
D-isocitrate
-
octameric wild-type enzyme without AMP and DTT, pH 7.4, 24C
1.01
-
D-isocitrate
-
octameric enzyme mutant IDH1G15D/IDH2 without AMP and DTT, pH 7.4, 24C
1.03
-
D-isocitrate
-
octameric enzyme mutant IDH1/IDH2C56S/C150S/C242S without AMP, with or without DTT, pH 7.4, 24C
1.19
-
D-isocitrate
-
octameric enzyme IDH1G15D/IDH2 without AMP, with DTT, pH 7.4, 24C
1.3
-
D-isocitrate
-
octameric enzyme mutant IDH1/IDH2C56S/C242S without AMP, with DTT, pH 7.4, 24C
1.6
-
D-isocitrate
-
octameric enzyme mutant IDH1/IDH2C56S/C242S without AMP and DTT, pH 7.4, 24C
7.9
-
D-isocitrate
-
-
62.2
-
D-isocitrate
-
-
0.075
-
DL-isocitrate
-
pH 7.5, 37C, recombinant wild-type enzyme
0.143
-
DL-isocitrate
-
pH 7.5, 37C, recombinant enzyme mutant S102G
0.148
-
DL-isocitrate
-
pH 7.5, 37C, recombinant enzyme mutant S102A
0.15
-
DL-isocitrate
-
pH 7.5, 37C, recombinant enzyme mutant S102T
0.385
-
DL-isocitrate
-
pH 7.5, 37C, recombinant enzyme mutant S102Y
0.0183
-
homoisocitrate
-
6fold His-tagged enzyme, at 70C in 50 mM N-2-hydroxyethylpiperadine-N0-2-ethanesulfonate-NaOH (pH 7.8), 0.2 M KCl, 0.2 mM MnCl2, 1mM NAD+
0.0164
-
Isocitrate
-
6fold His-tagged enzyme, at 70C in 50 mM N-2-hydroxyethylpiperadine-N0-2-ethanesulfonate-NaOH (pH 7.8), 0.2 M KCl, 0.2 mM MnCl2, 1mM NAD+
0.0517
-
Isocitrate
-
-
0.09
-
Isocitrate
-
pH 7.2, 25C, recombinant mutant betaY137E, in presence of 1 mM ADP
0.12
-
Isocitrate
-
pH 7.5
0.28
-
Isocitrate
-
pH 7.2, 25C, recombinant mutant betaY137F, in presence of 1 mM ADP
0.32
-
Isocitrate
-
purified recombinant wild-type enzyme, pH 7.2, 25C, in presence of 1 mM ADP
0.5
-
Isocitrate
-
pH 7.2, 25C, recombinant wild-type enzyme, in presence of 1 mM ADP
0.581
-
Isocitrate
-
pH 7.4, 25C
0.77
-
Isocitrate
-
purified recombinant mutant beta-R99Q, pH 7.2, 25C, in presence of 1 mM ADP
0.9
-
Isocitrate
-
purified recombinant mutant beta-R99Q, pH 7.2, 25C
0.92
-
Isocitrate
-
pH 7.2, 25C, recombinant mutant betaY137S, in presence of 1 mM ADP
1.2
-
Isocitrate
-
pH 7.2, 25C, recombinant mutant betaY137S
1.8
-
Isocitrate
-
purified recombinant mutant gamma-R97Q, pH 7.2, 25C, in presence of 1 mM ADP
1.8
-
Isocitrate
-
pH 7.2, 25C, recombinant mutant betaY137F
2
-
Isocitrate
-
purified recombinant mutant gamma-R97Q, pH 7.2, 25C
2
-
Isocitrate
-
pH 7.2, 25C, recombinant wild-type enzyme
2.2
-
Isocitrate
-
purified recombinant wild-type enzyme, pH 7.2, 25C
2.2
-
Isocitrate
-
25C, pH 7.2, wild-type enzyme; wild type enzyme in 20 mM isocitrate and 1mM MnSO4
2.4
-
Isocitrate
-
pH 7.2, wild-type enzyme
2.9
-
Isocitrate
-
pH 7.2, beta-subunit mutant enzyme D192N
3.4
-
Isocitrate
-
25C, pH 7.2, alpha-subunit mutant enzyme D234C; D234C, alpha-subunit mutant, in 20 mM isocitrate and 1mM MnSO4
3.4
-
Isocitrate
-
pH 7.2, 25C, recombinant mutant betaY137E
3.5
-
Isocitrate
-
25C, pH 7.2, alpha-subunit mutant enzyme D206N; D206N, alpha-subunit mutant, in 20 mM isocitrate and 1mM MnSO4
5.1
-
Isocitrate
-
25C, pH 7.2, beta-subunit mutant enzyme D217N; D217N, beta-subunit mutant, in 20 mM isocitrate and 1mM MnSO4
9.1
-
Isocitrate
-
pH 7.2, alpha-subunit mutant enzyme D181N
13
-
Isocitrate
-
pH 7.2, gamma-subunit mutant enzyme D190N
20
-
Isocitrate
-
25C, pH 7.2, alpha-subunit mutant enzyme D230C; D230C, alpha-subunit mutant, in 20 mM isocitrate and 1mM MnSO4
41
-
Isocitrate
-
25C, pH 7.2, gamma-subunit mutant enzyme D215N; D215N, gamma-subunit mutant, in 20 mM isocitrate and 1mM MnSO4
0.22
-
Mn2+
-
purified recombinant wild-type enzyme and mutant beta-R99Q, pH 7.2, 25C
0.004
-
NAD+
-
purified recombinant mutant gamma-R97Q, pH 7.2, 25C
0.014
-
NAD+
-
purified recombinant mutant beta-R99Q, pH 7.2, 25C
0.04
-
NAD+
-
25C, pH 7.2, alpha-subunit mutant enzyme D234C
0.06
0.09
NAD+
-
-
0.06
-
NAD+
-
pH 7.2, 25C, recombinant wild-type enzyme
0.066
-
NAD+
-
pH 8.0, 70C, mutant enzyme D328K
0.068
-
NAD+
-
pH 8.0, 70C, wild-type enzyme
0.0683
-
NAD+
-
pH 8.0, 70C, the Km-value for NADP+ is about 65fold higher than the KM-value for NAD+
0.07
-
NAD+
-
25C, pH 7.2, wild-type enzyme
0.073
-
NAD+
-
purified recombinant wild-type enzyme, pH 7.2, 25C
0.0771
-
NAD+
-
6fold His-tagged enzyme, at 70C in 50 mM N-2-hydroxyethylpiperadine-N0-2-ethanesulfonate-NaOH (pH 7.8), 0.2 M KCl, 0.2 mM MnCl2
0.08
-
NAD+
-
pH 7.2, wild-type enzyme
0.09
-
NAD+
-
pH 7.2, 25C, recombinant mutant betaY137E
0.099
-
NAD+
-
7-fold mutant
0.12
-
NAD+
-
pH 7.2, 25C, recombinant mutant betaY137F
0.136
-
NAD+
-
pH 7.4, 25C
0.14
-
NAD+
-
25C, pH 7.2, alpha-subunit mutant enzyme D206N
0.154
-
NAD+
-
pH 7.5, 37C, recombinant enzyme
0.18
-
NAD+
-, Q8GAX0
pH 9.0, 30C, native enzyme
0.19
-
NAD+
-
25C, pH 7.2, gamma-subunit mutant enzyme D215N
0.2
-
NAD+
-
pH 7.5
0.245
-
NAD+
-
pH 7.5, 37C, with Mn2+, recombinant enzyme
0.246
-
NAD+
-
pH 7.5, 37C, recombinant enzyme mutant S102A
0.25
-
NAD+
-
-
0.295
-
NAD+
-
pH 7.5, 37C, recombinant enzyme mutant S102G
0.312
-
NAD+
-
pH 7.5, 37C, with Mg2+, recombinant enzyme
0.33
-
NAD+
-
membrane-associated ICDH
0.336
-
NAD+
-
pH 8.0, 70C, mutant enzyme D328K/I329Y
0.35
-
NAD+
-
pH 7.5, 37C, recombinant enzyme mutant S102T
0.63
-
NAD+
-
pH 7.2, 25C, recombinant mutant betaY137S
0.68
-
NAD+
-
25C, pH 7.2, beta-subunit mutant enzyme D217N
0.71
-
NAD+
-
pH 7.2, beta-subunit mutant enzyme D192N
1.1
-
NAD+
-
25C, pH 7.2, alpha-subunit mutant enzyme D230C
1.2
-
NAD+
-
pH 7.2, alpha-subunit mutant enzyme D181N
1.5
-
NAD+
-
pH 7.2, gamma-subunit mutant enzyme D190N
1.56
-
NAD+
-
pH 7.5, 37C, recombinant enzyme mutant S102Y
4.7
-
NAD+
-
wild type
0.017
-
NADP+
-
wild type
0.162
-
NADP+
-
pH 8.0, 70C, mutant enzyme D328K
0.211
-
NADP+
-
pH 8.0, 70C, mutant enzyme D328K/I329Y
4.44
-
NADP+
-
pH 8.0, 70C, wild-type enzyme
5.8
-
NADP+
-
7-fold mutant
6.57
-
NADP+
-, Q8GAX0
pH 9.0, 30C, native enzyme
6.9
-
NADP+
-
-
7.7
-
NADP+
-
pH 7.5, 37C, with Mn2+, recombinant enzyme
8.2
-
NADP+
-
pH 7.5, 37C, with Mg2+, recombinant enzyme
0.39
-
Mn2+
-
purified recombinant mutant gamma-R97Q, pH 7.2, 25C
additional information
-
additional information
-, Q8GAX0
kinetic properties of the native and the recombinant enzyme are similar
-
additional information
-
additional information
-
kinetics and ligand binding
-
additional information
-
additional information
-
NAD+-specific D-isocitrate dehydrogenase is an allosterically regulated. AMP and NAD+ binding kinetics of enzyme mutants in presence or absence of DTT, overview; yeast NAD+-specific isocitrate dehydrogenase is an allosterically regulated
-
TURNOVER NUMBER [1/s]
TURNOVER NUMBER MAXIMUM[1/s]
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.27
-
D-isocitrate
-
D234C, alpha-subunit mutant, in 20 mM isocitrate and 1 mM MnSO4
2.49
-
D-isocitrate
-
D230C, alpha-subunit mutant, in 20 mM isocitrate and 1 mM MnSO4
11.8
-
D-isocitrate
-
D215N, gamma-subunit mutant, in 20 mM isocitrate and 1 mM MnSO4
19.6
-
D-isocitrate
-
D217N, beta-subunit mutant, in 20 mM isocitrate and 1 mM MnSO4
30
-
D-isocitrate
-
wild type enzyme in 20 mM isocitrate and 1 mM MnSO4
36.8
-
D-isocitrate
-
D206N, alpha-subunit mutant, in 20 mM isocitrate and 1 mM MnSO4
57.5
-
D-isocitrate
-
-
73
-
D-isocitrate
-
-
1.5
-
DL-isocitrate
-
pH 7.5, 37C, recombinant enzyme mutant S102Y
3.3
-
DL-isocitrate
-
pH 7.5, 37C, recombinant enzyme mutant S102A
4
-
DL-isocitrate
-
pH 7.5, 37C, recombinant enzyme mutant S102G
25
-
DL-isocitrate
-
pH 7.5, 37C, recombinant enzyme mutant S102T
124
-
DL-isocitrate
-
pH 7.5, 37C, recombinant wild-type enzyme
13.7
-
homoisocitrate
-
6fold His-tagged enzyme, at 70C in 50 mM N-2-hydroxyethylpiperadine-N0-2-ethanesulfonate-NaOH (pH 7.8), 0.2 M KCl, 0.2 mM MnCl2, 1 mM NAD+
0.27
-
Isocitrate
-
25C, pH 7.2, alpha-subunit mutant enzyme D234C
2.49
-
Isocitrate
-
25C, pH 7.2, alpha-subunit mutant enzyme D230C
11.8
-
Isocitrate
-
25C, pH 7.2, gamma-subunit mutant enzyme D215N
14.8
-
Isocitrate
-
6fold His-tagged enzyme, at 70C in 50 mM N-2-hydroxyethylpiperadine-N0-2-ethanesulfonate-NaOH (pH 7.8), 0.2 M KCl, 0.2 mM MnCl2, 1 mM NAD+
19.6
-
Isocitrate
-
25C, pH 7.2, beta-subunit mutant enzyme D217N
30
-
Isocitrate
-
25C, pH 7.2, wild-type enzyme
36.8
-
Isocitrate
-
25C, pH 7.2, alpha-subunit mutant enzyme D206N
0.27
-
NAD+
-
25C, pH 7.2, alpha-subunit mutant enzyme D234C
2.49
-
NAD+
-
25C, pH 7.2, alpha-subunit mutant enzyme D230C
3
-
NAD+
-
pH 7.5, 37C, recombinant enzyme mutant S102A
3.5
-
NAD+
-
pH 7.5, 37C, recombinant enzyme mutant S102Y
9.1
-
NAD+
-
pH 7.5, 37C, recombinant enzyme mutant S102G
11.8
-
NAD+
-
25C, pH 7.2, gamma-subunit mutant enzyme D215N
19.6
-
NAD+
-
25C, pH 7.2, beta-subunit mutant enzyme D217N
21.8
-
NAD+
-
6fold His-tagged enzyme, at 70C in 50 mM N-2-hydroxyethylpiperadine-N0-2-ethanesulfonate-NaOH (pH 7.8), 0.2 M KCl, 0.2 mM MnCl2
30
-
NAD+
-
25C, pH 7.2, wild-type enzyme
36.8
-
NAD+
-
25C, pH 7.2, alpha-subunit mutant enzyme D206N
45.1
-
NAD+
-, Q8GAX0
pH 9.0, 30C, native enzyme
56
-
NAD+
-
pH 7.5, 37C, recombinant wild-type enzyme
59
-
NAD+
-
pH 7.5, 37C, recombinant enzyme mutant S102T
60.4
-
NAD+
-
pH 8.0, 70C, wild-type enzyme
88
-
NAD+
-
pH 7.5, 37C, with Mg2+, recombinant enzyme
103.4
-
NAD+
-
pH 8.0, 70C, mutant enzyme D328K
105.6
-
NAD+
-
pH 8.0, 70C, mutant enzyme D328K/I329Y
112
-
NAD+
-
pH 7.5, 37C, with Mn2+, recombinant enzyme
14
-
NADP+
-
pH 7.5, 37C, with Mg2+, recombinant enzyme
21.3
-
NADP+
-, Q8GAX0
pH 9.0, 30C, native enzyme
25
-
NADP+
-
pH 7.5, 37C, with Mn2+, recombinant enzyme
61.3
-
NADP+
-
-
93
-
NADP+
-
pH 8.0, 70C, wild-type enzyme
133
-
NADP+
-
pH 8.0, 70C, mutant enzyme D328K
168
-
NADP+
-
pH 8.0, 70C, mutant enzyme D328K/I329Y
kcat/KM VALUE [1/mMs-1]
kcat/KM VALUE [1/mMs-1] Maximum
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.000004
-
DL-isocitrate
-
pH 7.5, 37C, recombinant enzyme mutant S102Y
849
0.000022
-
DL-isocitrate
-
pH 7.5, 37C, recombinant enzyme mutant S102A
849
0.000028
-
DL-isocitrate
-
pH 7.5, 37C, recombinant enzyme mutant S102G
849
0.00017
-
DL-isocitrate
-
pH 7.5, 37C, recombinant enzyme mutant S102T
849
0.00165
-
DL-isocitrate
-
pH 7.5, 37C, recombinant wild-type enzyme
849
0.000002
-
NAD+
-
pH 7.5, 37C, recombinant enzyme mutant S102Y
7
0.00001
-
NAD+
-
pH 7.5, 37C, recombinant enzyme mutant S102A
7
0.00003
-
NAD+
-
pH 7.5, 37C, recombinant enzyme mutant S102G
7
0.00017
-
NAD+
-
pH 7.5, 37C, recombinant enzyme mutant S102T
7
0.0003
-
NAD+
-
pH 7.5, 37C, with Mg2+, recombinant enzyme
7
0.00036
-
NAD+
-
pH 7.5, 37C, recombinant enzyme
7
0.0005
-
NAD+
-
pH 7.5, 37C, with Mn2+, recombinant enzyme
7
314
-
NAD+
-
pH 8.0, 70C, mutant enzyme D328K/I329Y
7
888
-
NAD+
-
pH 8.0, 70C, wild-type enzyme
7
1567
-
NAD+
-
pH 8.0, 70C, mutant enzyme D328K
7
0.000002
-
NADP+
-
pH 7.5, 37C, with Mg2+, recombinant enzyme
10
0.000003
-
NADP+
-
pH 7.5, 37C, with Mn2+, recombinant enzyme
10
20.9
-
NADP+
-
pH 8.0, 70C, wild-type enzyme
10
796
-
NADP+
-
pH 8.0, 70C, mutant enzyme D328K/I329Y
10
821
-
NADP+
-
pH 8.0, 70C, mutant enzyme D328K
10
Ki VALUE [mM]
Ki VALUE [mM] Maximum
INHIBITOR
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.063
-
NADH
-
pH 7.4, 25C
0.18
-
NADH
-
pH 7.5
0.26
-
NADPH
-
pH 7.5
SPECIFIC ACTIVITY [µmol/min/mg]
SPECIFIC ACTIVITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
0.084
-
-
mitochondria from green leaves, forward reaction
0.092
-
-
partially purified enzyme, idh-II mutant
0.096
-
-
mitochondria from etiolated leaves, forward reaction
0.15
-
-
enzyme extract of cells in exponential growth phase
0.16
-
-
enzyme extract of cells in stationary growth phase
0.169
-
-
partially purified enzyme, wild-type
0.17
-
-
enzyme extract of cells in growth phase with acid synthesis
0.2
-
-
D234C, alpha-subunit mutant, in 20 mM D-isocitrate and 1 mM MnSO4
1.4
-
-
D230C, alpha-subunit mutant, in 20 mM D-isocitrate and 1 mM MnSO4
1.7
-
-
-
2.2
-
-
purified recombinant mutant gamma-R97Q
2.9
-
-
-
3.7
-
-
D215N, gamma-subunit mutant, in 20 mM D-isocitrate and 1 mM MnSO4
7.3
-
-
D217N, beta-subunit mutant, in 20 mM D-isocitrate and 1 mM MnSO4
13.5
-
-
purified recombinant mutant beta-R99Q
21.7
-
-
purified recombinant wild-type enzyme
22
-
-
purified enzyme
22
-
-
wild type enzyme, in 20 mM D-isocitrate and 1 mM MnSO4
27
31
-
-
29
-
-
D206N, alpha-subunit mutant, in 20 mM D-isocitrate and 1 mM MnSO4
50.5
-
-
with 0.12 mM NADP+ and 2 mM D-isocitrate
75.5
-
-
with 0.12 mM NADP+ and 2 mM D-isocitrate
120
-
-, Q8GAX0
purified native enzyme
additional information
-
-
no activity on 3-isopropylmalate
pH OPTIMUM
pH MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
6.5
-
-
-
7
7.2
-
-
7.2
-
-
assay at
7.4
-
-
assay at
7.5
-
-
-
7.5
-
-
assay at
8
-
-
assay at
8
-
-
with Mn2+
8.1
-
-
vertebrate muscle
8.4
-
-
-
8.5
-
-
with Mg2+
pH RANGE
pH RANGE MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
5.5
8.6
-
-
6
8
-
-
6
8.5
-
-
6.5
10
-
activity range, profile overview
7.2
9.2
-
activity range, profile overview
TEMPERATURE OPTIMUM
TEMPERATURE OPTIMUM MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
22
-
-
-
25
-
-
assay condition
25
-
-
assay at
25
-
-
assay at
25
-
-
assay at
25
-
-
assay at
30
-
-, Q8GAX0
assay at
70
-
-
assay at
TEMPERATURE RANGE
TEMPERATURE MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
12
37
-
-
25
55
-
activity range, profile overview
25
60
-
and above, activity range, profile overview
80
95
-
activity at 80C is about 50% compared to the activity at 90C
SOURCE TISSUE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
SOURCE
-, O81796, P93032, Q8LFC0, Q8LG77, Q945K7
-
Manually annotated by BRENDA team
-, O81796, P93032, Q8LFC0, Q8LG77, Q945K7
;
Manually annotated by BRENDA team
-, O81796, P93032, Q8LFC0, Q8LG77, Q945K7
-
Manually annotated by BRENDA team
-, O81796, P93032, Q8LFC0, Q8LG77, Q945K7
-
Manually annotated by BRENDA team
Arabidopsis thaliana Landsberg
-
-
-
Manually annotated by BRENDA team
-, O81796, P93032, Q8LFC0, Q8LG77, Q945K7
-
Manually annotated by BRENDA team
-, O81796, P93032, Q8LFC0, Q8LG77, Q945K7
-
Manually annotated by BRENDA team
-
green and etiolated
Manually annotated by BRENDA team
-, O81796, P93032, Q8LFC0, Q8LG77, Q945K7
; in leaves, the IDH genes are highly expressed in the veins, and to a lesser extent in mesophyll cells. Cauline leaf, rosette, juvenile leaf, adult leaf; in leaves, the IDH genes are highly expressed in the veins, and to a lesser extent in mesophyll cells. Cauline leaf, rosette, juvenile leaf, adult leaf, senescent leaf; in leaves, the IDH genes are highly expressed in the veins, and to a lesser extent in mesophyll cells. Cauline leaf, rosette, juvenile leaf, adult leaf, senescent leaf; in leaves, the IDH genes are highly expressed in the veins, and to a lesser extent in mesophyll cells. Cauline leaf, rosette, juvenile leaf, adult leaf, senescent leaf
Manually annotated by BRENDA team
Arabidopsis thaliana Landsberg
-
-
-
Manually annotated by BRENDA team
-
breast muscle
Manually annotated by BRENDA team
-
flight muscle
Manually annotated by BRENDA team
-
skeletal muscle
Manually annotated by BRENDA team
-, O81796, P93032, Q8LFC0, Q8LG77, Q945K7
-
Manually annotated by BRENDA team
-, O81796, P93032, Q8LFC0, Q8LG77, Q945K7
-
Manually annotated by BRENDA team
-, O81796, P93032, Q8LFC0, Q8LG77, Q945K7
-
Manually annotated by BRENDA team
-
from liquid shaker cultures
Manually annotated by BRENDA team
Arabidopsis thaliana Landsberg
-
from liquid shaker cultures
-
Manually annotated by BRENDA team
-, O81796, P93032, Q8LFC0, Q8LG77, Q945K7
-
Manually annotated by BRENDA team
-, O81796, P93032, Q8LFC0, Q8LG77, Q945K7
At4g35650 is not expressed in vegetative organs but is mainly expressed in the pollen
Manually annotated by BRENDA team
-, O81796, P93032, Q8LFC0, Q8LG77, Q945K7
-
Manually annotated by BRENDA team
-, O81796, P93032, Q8LFC0, Q8LG77, Q945K7
lateral root and elongation zone; lateral root and elongation zone; lateral root and elongation zone; lateral root and elongation zone
Manually annotated by BRENDA team
Arabidopsis thaliana Landsberg
-
-
-
Manually annotated by BRENDA team
-, O81796, P93032, Q8LFC0, Q8LG77, Q945K7
;
Manually annotated by BRENDA team
-, O81796, P93032, Q8LFC0, Q8LG77, Q945K7
-
Manually annotated by BRENDA team
-, O81796, P93032, Q8LFC0, Q8LG77, Q945K7
-
Manually annotated by BRENDA team
-, O81796, P93032, Q8LFC0, Q8LG77, Q945K7
apex; apex; apex; apex
Manually annotated by BRENDA team
-, O81796, P93032, Q8LFC0, Q8LG77, Q945K7
-
Manually annotated by BRENDA team
-, O81796, P93032, Q8LFC0, Q8LG77, Q945K7
-
Manually annotated by BRENDA team
Arabidopsis thaliana Landsberg
-
-
-
Manually annotated by BRENDA team
PDB
SCOP
CATH
ORGANISM
Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
MOLECULAR WEIGHT
MOLECULAR WEIGHT MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
32850
-
-, O81796, P93032, Q8LFC0, Q8LG77, Q945K7
IDH IV, without the predicted mitochondrial target peptide, calculated from sequence of amino acids
35910
-
-, O81796, P93032, Q8LFC0, Q8LG77, Q945K7
IDH III, without the predicted mitochondrial target peptide, calculated from sequence of amino acids
36040
-
-, O81796, P93032, Q8LFC0, Q8LG77, Q945K7
IDH VI, without the predicted mitochondrial target peptide, calculated from sequence of amino acids
36200
-
-, O81796, P93032, Q8LFC0, Q8LG77, Q945K7
IDH V, without the predicted mitochondrial target peptide, calculated from sequence of amino acids
36810
-
-, O81796, P93032, Q8LFC0, Q8LG77, Q945K7
IDH II, without the predicted mitochondrial target peptide, calculated from sequence of amino acids
37500
-
-
IDH2, SDS-PAGE
38000
-
-
IDH1, SDS-PAGE
38000
-
-
subunit IDH1, nonreducing PAGE
38900
-
-, O81796, P93032, Q8LFC0, Q8LG77, Q945K7
IDH I, without the predicted mitochondrial target peptide, calculated from sequence of amino acids
39590
-
-, O81796, P93032, Q8LFC0, Q8LG77, Q945K7
IDH II, with the predicted mitochondrial target peptide, calculated from sequence of amino acids
39630
-
-, O81796, P93032, Q8LFC0, Q8LG77, Q945K7
IDH I, with the predicted mitochondrial target peptide, calculated from sequence of amino acids
39960
-
-, O81796, P93032, Q8LFC0, Q8LG77, Q945K7
IDH III, with the predicted mitochondrial target peptide, calculated from sequence of amino acids
40580
-
-, O81796, P93032, Q8LFC0, Q8LG77, Q945K7
IDH VI, with the predicted mitochondrial target peptide, calculated from sequence of amino acids
40620
-
-, O81796, P93032, Q8LFC0, Q8LG77, Q945K7
IDH V, with the predicted mitochondrial target peptide, calculated from sequence of amino acids
45000
-
-
IDHa, SDS-PAGE
70000
-
-
recombinant enzyme, gel filtration
70000
-
-
analytical ultracentrifugation
74000
-
-
recombinant His6-tagged enzyme, gel filtration
90000
-
-, Q8GAX0
gel filtration and native PAGE
123000
-
-
disulfide bonded form of subunit IDH2, nonreducing PAGE
145000
-
-
gel filtration
191800
-
-
gel filtration
224000
-
-
ultracentrifugation
238000
-
-
gel filtration
245000
-
-
sedimentation equilibrium analysis
250000
-
-
Superose 6 gel filtration
260000
-
-
dynamic light scattering
290000
-
-
Superdex 200 gel filtration
300000
340000
-
gel filtration
303000
-
-
sequence calculation
315000
-
-
about, recombinant wild-type and mutant enzymes, gel filtration
320000
-
-
gel filtration
320000
-
-
gel filtration
335000
-
P28241, P28834
gel filtration; wild-type enzyme, gel filtration; wild-type enzyme, gel filtration
338000
-
-
gel filtration
412000
-
-
gel filtration
SUBUNITS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
dimer
-
alphabeta, 1 * 39000 + 1 * 41000, SDS-PAGE
dimer
-, Q8GAX0
2 * 45000, SDS-PAGE
dimer
-
2 * 46000, recombinant His6-tagged enzyme, SDS-PAGE
dimer
Acidithiobacillus thiooxidans ON107
-
2 * 45000, SDS-PAGE
-
dimer
Zymomonas mobilis ATCC10988
-
2 * 46000, recombinant His6-tagged enzyme, SDS-PAGE
-
heterotetramer
-
2 * 37000, 1 * 39000, 1 * 39000
heterotetramer
-
determination of secondary structure by circular dichroism, subunit molar ratio of wild-type and mutant NAD-IDHs, overview
homodimer
-
2 * 44300, calculated from sequence
octamer
-
alpha4beta4, IDH1 and IDH2, 4 * 38001 + 4 * 37755, SDS-PAGE
octamer
-
8 * 45000, SDS-PAGE
octamer
-
alpha8, 8 * 40500, SDS PAGE, ICDH-1 and ICDH-2
octamer
-
8 * 52000, SDS-PAGE
octamer
-
alpha4beta4, subunits are termed IDH1 and IDH2
octamer
-
8 * 38000
octamer
P28241, P28834
4 * 38001, 4 * 37755, the enzyme consists of four IDH1 and four IDH2 subunits, the basic structural unit of the enzyme is an IDH1/IDH2 heterodimer; 4 * IDH1 + 4 * IDH2; 4 * IDH1 + 4 * IDH2
octamer
-
the octameric enzyme is composed of four heterodimers of regulatory IDH1 and catalytic IDH2 subunits
octamer
-
4 * regulatory IDH1 + 4 * catalytic IDH2 subunits
octamer
-
4 * 38001, subunit IDH1, + 4 * 37755, subunit IDH2, sequence calculation; the enzyme is composed of four heterodimers of a catalytic IDH2 subunit and a regulatory IDH1 subunit
octamer
Saccharomyces cerevisiae MMY011
-
4 * 38001, 4 * 37755, the enzyme consists of four IDH1 and four IDH2 subunits, the basic structural unit of the enzyme is an IDH1/IDH2 heterodimer; the octameric enzyme is composed of four heterodimers of regulatory IDH1 and catalytic IDH2 subunits
-
tetramer
-
-
tetramer
-
alpha2betagamma, 4 * 39000-41000, SDS-PAGE
tetramer
-
4 * 36340, the clasp-like domain of McIDH is a likely site for tetramerization, calculated from sequence
trimer
-
3 * 83181, calculated from amino acid sequence
monomer
-
1 * 80000, SDS-PAGE
additional information
-
model of binding sites for isocitrate of the 2 different subunits
additional information
-
enzyme subunit ratio of recombinant wild-type and mutant enzymes, overview
additional information
-
subunit IDH-I can substitute for a deficient mutant subunit IDH-II
additional information
-
the ratios of the alpha-, beta-, and gamma-subunits of the wild-type and three mutant enzymes all approximate 2:1:1
additional information
-
subunit IDH2 contains catalytic isocitrate/Mg2+ and NAD+ binding sites whereas subunit IDH1 contains homologous binding sites, respectively, for cooperative binding of isocitrate and for allosteric binding of AMP. The subsunits share 42% sequence identity
additional information
-
the enzyme is composed of four heterodimers, in two heterotetramers, of a catalytic IDH2 subunit and a regulatory IDH1 subunit, IDH octamer structure, overview
additional information
Arabidopsis thaliana Landsberg
-
subunit IDH-I can substitute for a deficient mutant subunit IDH-II
-
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
phosphoprotein
-
catalytically important phosphorylation site at Ser102
glycoprotein
-
-
Crystallization/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
recombinant isocitrate dehydrogenase complexed with NAD+ and citrate solved to a resolution of 1.9 A, hanging drop vapor diffusion method
-
crystallization in artificial mother liquor supplemented with 100 mM NAD+
-
sitting drop vapour diffusion method, using 3-5% (w/v) PEG 20000, 0.1 M MES pH 5.7 and 0.2 M CaCl2
-
hanging drop vapor diffusion method
-
pH STABILITY
pH STABILITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
5.5
8.5
-
-
TEMPERATURE STABILITY
TEMPERATURE STABILITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
0
-
-
full loss in activity in a few hours
40
-
-
purified recombinant His-tagged enzyme, rapid inactivation above
40
-
-
purified recombinant enzyme, stable up to, rapid inactivation above
42
-
-
10 min, 50% loss in activity
50
-
-
purified recombinant enzyme, inactivation
55
-
-, Q8GAX0
stable up to
70
-
-, Q8GAX0
inactivation after 30 min
70
-
-
apparent midpoint melting temperature
102
-
-
the apparent melting temperature is 102.3C, mutant enzyme D328K
103
-
-
the apparent melting temperature is 102.9C, mutant enzyme D328K/I329Y
104
-
-
the apparent melting temperature is 103.7C, wild-type enzyme
104
-
-
the Tm-value is 103.7C
additional information
-
-
thermal denaturation is an irreversible process
GENERAL STABILITY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
ICDH-2 is more stable to urea than ICDH-1
-
20 h in medium containing ADP
Sarcophaga barbata, waterbug
-
20% glycerol stabilizes during storage
-
STORAGE STABILITY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
-90C, no loss of activity after 6 weeks
-
-80C, partially purified enzyme, several months, stable
-
4C, glycerol 20%, 35-40% of original activity after 96 h, membrane-associated ICDH
-
4C, recombinant wild-type enzyme, in affinity elution buffer containing 50 mM sodium phosphate, pH 7.5, 300 mM NaCl, and 200 mM imidazole, stable for several weeks
-
-90C, no loss of activity after 6 weeks
-
Purification/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
multi-step purification of the native enzyme, 520fold to homogeneity, partial purification of the recombinant enzyme from Escherichia coli
-, Q8GAX0
mitochondrial preparation
-
Ni2+-affinity chromatography
-
Ni2+-affinity chromatography
-
ammonium sulfate fractionation and gel filtration
-
recombinant wild-type and mutant enzymes from Escherichia coli
-
recombinant wild-type and mutant NAD-IDHs from Escherichia coli by ammonium sulfate fractionation, anion exchange chromatography, ultrafiltration, and gel filtration
-
Hi-Trap chelating column chromatography and Superdex 200 gel filtration
-
partially by mitochondrion isolation in a Percoll gradient, and ammonium sulfate precipitation in the 60-80% fraction, DEAE cellulose chromatography, and desalting
-
gel filtration
-
Hi-Trap chelating HP column chromatography
-
Ni-NTA column chromatography
-
Ni2+-nitrilotriacetate (Ni2+-NTA) column chromatography
P28241, P28834
Ni2+-nitrilotriacetic acid resin chromatography
-
Ni2+-nitrilotriacetic acid superflow resin chromatography
-
recombinant His-tagged enzyme from Escherichia coli strain BL21-Gold(DE3) by nickel affinity chromatography
-
recombinant His-tagged wild-type and mutant enzymes from strain IDH12DELTAL by nickel affinity chromatography
-
recombinant wild-type and mutant enzymes from Escherichia coli
-
129fold to homogeneity by ammonium sulfate fractionation, hydrophobic chromatography on an octyl resin, and gel filtration
-
recombinant His6-tagged enzyme from Escherichia coli strain BL21 (DE3)
-
Cloned/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
gene icd, DNA and amino acid sequence determination and analysis, expression in enzyme-deficient Escherichia coli strain EB106
-, Q8GAX0
expressed in Saccharomyces cerevisiae
-, O81796, P93032, Q8LFC0, Q8LG77, Q945K7
expressed in Escherichia coli
-
expressed in Escherichia coli
-
expression in Escherichia coli
-
expression of wild-type and mutant NAD-IDHs in Escherichia coli
-
genotyping in diverse cancer cell lines, overview
-
overexpression of the wild-type and a mutant enzyme, the latter containing the wild-type 2 subunits alpha and beta plus an additional third one, gamma, overexpression of the 3-subunit mutant and the same mutant with point mutations of Arg-residues in Escherichia coli
-
cloned and overexpressed in Escherichia coli
-
expressed in Escherichia coli BL21(DE3)RP cells
-
expressed in Escherichia coli strain BL21-CodonPlus (DE3)-RIL
-
gene RtIDH1, DNA and amino acid sequence determination and analysis, sequence comparison, expression in the Saccharomyces cerevisiae strain BY4741 idhDELTA mutant, RtIdh expression leads to increased intracellular lipid content and extracellular citrate concentration with increasing carbon/nitrogen molar ratio of the media under nitrogen limiting conditions; gene RtIDH2, DNA and amino acid sequence determination and analysis, sequence comparison, expression in the Saccharomyces cerevisiae strain BY4741 idhDELTA mutant, RtIdh expression leads to increased intracellular lipid content and extracellular citrate concentration with increasing carbon/nitrogen molar ratio of the media under nitrogen limiting conditions
G1APK2, G1APK3, -
expressed in Escherichia coli BL21-Gold (DE3) cells
-
expression of His-tagged wild-type and mutant enzymes in yeast strain IDH12DELTAL deficient in both subunits of the enzyme
-
His-tagged enzyme expression in Escherichia coli strain BL21-Gold(DE3)
-
wild-type and mutant enzymes are expressed in a idh1DELTAidh2DELTA yeast strain which contains deletion/insertion mutations in genomic IDH1 and IDH2 loci; wild-type and mutant enzymes are expressed in a idh1DELTAidh2DELTA yeast strain which contains deletion/insertion mutations in genomic IDH1 and IDH2 loci
P28241, P28834
gene SlIDH1, DNA and amino acid sequence determination and analysis, phylogenetic analysis, expression in antisense orientation in tomato plants
-
gene idh, expression of wild-type and mutant enzymes in Escherichia coli glutamate auxotrophic strain Dicd::kanr fused to gene icd, the endogenous icd gene is replaced by the kanamycin resistance gene, the wild-type phenotype of the icd defective strain on minimal medium without glutamate is restored
-
DNA and amino acid sequence determination and analysis, genotyping and sequence comparison with the acient ancestor teosinte, Zea mays ssp. Parviglumis, overview
-
gene idh, DNA and amino acid sequence determination and analysis, sequence comparisons, expression of His6-tagged enzyme in Escherichia coli strain BL21 (DE3)
-
ENGINEERING
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
C201M/C332Y/K344D/Y345I/V351A/Y391K/R395S
-
converts the cofactor specificity from 7000-fold preference of NADP+ to a 200-fold preference of NAD+
alphaY126E
-
site-directed mutagenesis of subunit alpha, almost inactive mutant, shows low activity at pH 6.1 instead of pH 7.2, Km,Mn2+ is 30fold higher in the alphaY126E mutant as compared with the wild-type. Km,NAD+ for the alphaY126E mutant is 29fold higher than that of the wild-type. The Vmax of the wild-type at pH 6.1 is 0.0144 mmol/min/mg, whereas that for the alphaY126E mutant is only 0.00103 mmol/min/mg, suggesting a critical role for the residue in enzyme activity
alphaY126F
-
site-directed mutagenesis of subunit alpha, inactive mutant
alphaY126S
-
site-directed mutagenesis of subunit alpha, inactive mutant
betaY137E
-
site-directed mutagenesis of subunit beta, the mutant shows reduced activity compared to the wild-type enzyme
betaY137F
-
site-directed mutagenesis of subunit beta, the mutant shows reduced activity compared to the wild-type enzyme
betaY137S
-
site-directed mutagenesis of subunit beta, the mutant shows reduced activity compared to the wild-type enzyme
D181N
-
mutation in the alpha-subunit exhibits a 2000fold decrease in Vmax, with increases of 15fold in the Kms for Mn2+ and NAD+ and a much smaller change in the Km for isocitrate. Mutant enzyme fails to respond to ADP by lowering the Km for isocitrate, although it binds to ADP
D190N
-
mutation in the gamma-subunit results in 4-5fold decrease in Vmax as compared to wild-type enzyme. The Km-values for NAD+ and for Mn2+ of the mutant enzyme are 19 and 72 times, respectively, that of the wild-type enzyme with a much smaller effect on the Km for isocitrate. Mutant enzyme fails to respond to ADP by lowering the Km for isocitrate, although it binds to ADP
D192N
-
mutation in the beta-subunit results in 4-5fold decrease in Vmax as compared to wild-type enzyme. The Km-value for NAD+ of the mutant enzyme is 9times that of the normal enzyme with little or no effect on the affinity for Mn2+ or isocitrate. Mutant enzyme fails to respond to ADP by lowering the Km for isocitrate, although it binds to ADP
D206N
-
alpha-subunit mutant; specific activity of the alpha-subunit mutant enzyme is 1.3fold higher than specific activity of wild-type enzyme
D215N
-
gamma-subunit mutant; specific activity of the gamma-subunit mutant enzyme is 17% of specific activity of wild-type enzyme. 100fold increase in KM-value for Mn2+. Km-value for isocitrate is elevated
D217N
-
beta-subunit mutant; specific activity of the beta-subunit mutant enzyme is 33% of specific activity of wild-type enzyme. 16fold increase in KM-vlaue for NAD+
D230C
-
alpha-subunit mutant; specific activity of the alpha-subunit mutant enzyme is 6% of specific activity of wild-type enzyme. 32fold increase in KM-value for Mn2+. Km-value for isocitrate is elevated. 16fold increase in KM-vlaue for NAD+
D230N
-
alpha-subunit mutant; mutation in alpha-subunit results in complete loss of activity
D234C
-
alpha-subunit mutant; specific activity of the alpha-subunit mutant enzyme is 1% of specific activity of wild-type enzyme
D234N
-
alpha-subunit mutant; mutation in alpha-subunit results in complete loss of activity
gammaY135F
-
site-directed mutagenesis of subunit gamma, inactive mutant
R132C
-
naturally occuring IDH1 mutation
R132G
-
naturally occuring IDH1 mutation
R132H
-
naturally occuring IDH1 mutation
R132L
-
naturally occuring IDH1 mutation
R132S
-
naturally occuring IDH1 mutation
R132V
-
naturally occuring IDH1 mutation
R88Q
-
site-directed mutagenesis, residue of the alpha-subunit, inactive mutant
R97Q
-
site-directed mutagenesis, residue of the additional mutant gamma-subunit, highly reduced activity compared to the wild-type enzyme
R99Q
-
site-directed mutagenesis, residue of the beta-subunit, reduced activity compared to the wild-type enzyme
D328K
-
the mutant shows dual coenzyme specificity
D328K/I329Y
-
introduction of the double mutation shifts the cofactor preference from NAD+ to NADP+
A108R/F136Y/T241D/N245D
-
site-directed mutagenesis, residues of subunit IDH1 mutant is unable to bind AMP, ligand-binding analysis
A108R/F136Y/T241D/N245D/R114A/Y142F/D248T/D252N
-
site-directed mutagenesis, residues of subunit IDH1 are A108R, F136Y, T241D, and N245D, residues of subunit IDH2 are R114A, Y142F, D248T, and D252N, mutant is unable to bind AMP, ligand-binding analysis
C150S
-
insensitive to treatment with diamide, the presence of the IDH2 Cys-150 residue (and perhaps the potential for disulfide bond formation) may contribute to cooperativity and may also limit maximal IDH activity
C150S
-
site-directed mutagenesis of subunit IDH2, disulfide bridge formation by C150 is abolished
C150S
-
an octameric IDH1/IDH2C150S mutant enzyme, that shows unaltered activity and similar kinetics compared to the wild-type enzyme; site-directed mutagenesis, IDH1/IDH2C150S octameric enzyme
C56S/C150S/C242S
-
site-directed mutagenesis, IDH1/IDH2C150S octameric enzyme
C56S/C242S
-
shows activity similar to wild type enzyme and is sensitive to treatment with diamide
C56S/C242S
-
site-directed mutagenesis of subunit IDH2, the mutation does not affect disulfide formation in the enzyme
C56S/C242S
-
an octameric IDH1/IDH2C56S/C242S mutant enzyme, the mutant enzyme shows a reduction in Vmax relative to that of the wild-type enzyme of about 50%, although about 30% activity is restored in the presence of dithiothreitol; site-directed mutagenesis, IDH1/IDH2C150S octameric enzyme
D279A
-
IDH1D279A
D279A
-
site-directed mutagenesis of subunit IDH1, the mutation results in a loss of activation by AMP
D279A/D280A
-
site-directed mutagenesis, mutation of a IDH1 residue, reduced AMP binding, ligand-binding analysis
D286A
-
IDH2D286A
D286A
-
site-directed mutagenesis of subunit IDH2, the mutation results in a dramatic reduction in Vmax primarily due to a 70fold increase in the S0.5 value for NAD+
D286A/I287A
-
site-directed mutagenesis, mutation of a IDH2 residue, highly reduced NAD+ binding, ligand-binding analysis
G15D
-
site-directed mutagenesis of subunit IDH1, the tetrameric IDH1G15D/IDH2 enzyme exhibits half-site binding (two sites) for isocitrate in the absence of DTT and full-site binding (four sites) in the presence of DTT
G15D
-
a tetrameric IDH1G15D/IDH2 mutant enzyme, that shows reduced activity and altered kinetics compared to the wild-type enzyme
H281A
-
site-directed mutagenesis, mutation of a IDH2 residue, mutant cannot bind NAD+, ligand-binding analysis
I221A
P28241, P28834
residue changes in IDH2 subunits
I221A/V225A/V229A
P28241, P28834
mutant enzyme IDH1-IDH2(I221A/V225A/V229A) shows an about 6fold decrease in apparent affinity for isocitrate measured in the absence or presence of AMP as compared to wild-type enzyme. Mutant enzyme IDH1-IDH2 (I221A/V225A/V229A) exhibits a moderate decrease in apparent affnity for cofactor (about 2.5fold relative to wild-type) in the absence of AMP. The mutant enzyme has acquired the novel property of cooperativity with respect to NAD+, but this cooperativity is not apparent in the presence of AMP. The mutant enzyme with residue changes in only one subunit are active in vivo; mutant enzyme IDH1-IDH2(I221A/V225A/V229A) shows an about 6fold decrease in apparent affinity for isocitrate measured in the absence or presence of AMP as compared to wild-type enzyme. Mutant enzyme IDH1-IDH2 (I221A/V225A/V229A) exhibits a moderate decrease in apparent affnity for cofactor (about 2.5fold relative to wild-type) in the absence of AMP. The mutant enzyme has acquired the novel property of cooperativity with respect to NAD+, but this cooperativity is not apparent in the presence of AMP. The mutant enzyme with residue changes in only one subunit are active in vivo
I280A
-
IDH1I280A
I280A
-
site-directed mutagenesis of subunit IDH1, the mutation results in a loss of activation by AMP
I287A
-
IDH1I287A
I287A
-
site-directed mutagenesis of subunit IDH2, the mutation results in a dramatic reduction in Vmax primarily due to a 70fold increase in the S0.5 value for NAD+
K171L
-
mutant IDH1K171L
R114A/Y142F/D248T/D252N
-
site-directed mutagenesis, residues of subunit subunit IDH2, ligand-binding analysis
R274A
-
site-directed mutagenesis, mutation of a IDH1 residue, reduced AMP binding, ligand-binding analysis
S220A
P28241, P28834
residue changes in IDH1 subunits
S92A
-
site-directed mutagenesis, residue of subunit IDH1, reduction of isocitrate substrate binding sites by half, detrimental effects on isocitrate binding and respective kinetic defects in catalysis and allosteric activation by AMP, ligand-binding analysis
S92A/S98A
-
site-directed mutagenesis, residue of subunit IDH1 is S92, residue of subunit IDH2 is S98, ligand-binding analysis
S98A
-
site-directed mutagenesis, residue of subunit IDH2, reduction of isocitrate substrate binding sites by half, detrimental effects on isocitrate binding and respective kinetic defects in catalysis and allosteric activation by AMP, ligand-binding analysis
V214A
P28241, P28834
residue changes in IDH1 subunits
V216A/S220A/V224A
P28241, P28834
IDH1(V216A/S220A/V224A)IDH2 mutant enzyme shows an about 6fold decrease in apparent affinity for isocitrate measured in the absence or presence of AMP as compared to wild-type enzyme. IDH1(V216A/S220A/V224A)IDH2 mutant enzyme exhibits a moderate decrease in apparent affnity for cofactor (about 2.5fold relative to wild-type) in the absence of AMP. The mutant enzyme has acquired the novel property of cooperativity with respect to NAD+, but this cooperativity is not apparent in the presence of AMP. The mutant enzyme with residue changes in only one subunit are active in vivo; IDH1(V216A/S220A/V224A)IDH2 mutant enzyme shows an about 6fold decrease in apparent affinity for isocitrate measured in the absence or presence of AMP as compared to wild-type enzyme. IDH1(V216A/S220A/V224A)IDH2 mutant enzyme exhibits a moderate decrease in apparent affnity for cofactor (about 2.5fold relative to wild-type) in the absence of AMP. The mutant enzyme has acquired the novel property of cooperativity with respect to NAD+, but this cooperativity is not apparent in the presence of AMP. The mutant enzyme with residue changes in only one subunit are active in vivo
V216A/S220A/V224A/I221A/V225A/V229A
P28241, P28834
in the absence of AMP, the IDH1(V216A/S220A/V224A)-IDH2(I221A/V225A/V229A) mutant enzyme demonstrates an about 30fold decrease in apparent Vmax relative to wild-type and a loss of cooperativity with respect to isocitrate and, in the presence of AMP, the apparent affinity of the enzyme for isocitrate is 35fold lower than that of the wild-type enzyme. This mutant enzyme also exhibits a significant decrease in apparent affinity for NAD+ (about 30fold in the absence of AMP and about 10fold in the presence of AMP relative to wild-type). The mutant enzyme has acquired the novel property of cooperativity with respect to NAD+, but this cooperativity is not apparent in the presence of AMP. The mutant enzyme demonstrates decreases in apparent affnity for isocitrate of about 12fold in the absence of AMP and of about 26fold in the presence of AMP relative to wild-type. For this mutant enzyme, with respect to isocitrate, allosteric activation by AMP and cooperativity in the absence of AMP are no longer apparen. The mutant enzyme is not fully functional in vivo; in the absence of AMP, the IDH1(V216A/S220A/V224A)-IDH2(I221A/V225A/V229A) mutant enzyme demonstrates an about 30fold decrease in apparent Vmax relative to wild-type and a loss of cooperativity with respect to isocitrate and, in the presence of AMP, the apparent affinity of the enzyme for isocitrate is 35fold lower than that of the wild-type enzyme. This mutant enzyme also exhibits a significant decrease in apparent affinity for NAD+ (about 30fold in the absence of AMP and about 10fold in the presence of AMP relative to wild-type). The mutant enzyme has acquired the novel property of cooperativity with respect to NAD+, but this cooperativity is not apparent in the presence of AMP. The mutant enzyme demonstrates decreases in apparent affnity for isocitrate of about 12fold in the absence of AMP and of about 26fold in the presence of AMP relative to wild-type. For this mutant enzyme, with respect to isocitrate, allosteric activation by AMP and cooperativity in the absence of AMP are no longer apparen. The mutant enzyme is not fully functional in vivo
V224A
P28241, P28834
residue changes in IDH1 subunits
V225A
P28241, P28834
residue changes in IDH2 subunits
V229A
P28241, P28834
residue changes in IDH2 subunits
C150S
Saccharomyces cerevisiae MMY011
-
insensitive to treatment with diamide, the presence of the IDH2 Cys-150 residue (and perhaps the potential for disulfide bond formation) may contribute to cooperativity and may also limit maximal IDH activity
-
C56S/C242S
Saccharomyces cerevisiae MMY011
-
shows activity similar to wild type enzyme and is sensitive to treatment with diamide
-
D279A
Saccharomyces cerevisiae MMY011
-
IDH1D279A
-
D286A
Saccharomyces cerevisiae MMY011
-
IDH2D286A
-
I221A
Saccharomyces cerevisiae MMY011
-
residue changes in IDH2 subunits
-
I280A
Saccharomyces cerevisiae MMY011
-
IDH1I280A
-
K171L
Saccharomyces cerevisiae MMY011
-
mutant IDH1K171L
-
S220A
Saccharomyces cerevisiae MMY011
-
residue changes in IDH1 subunits
-
S92A
Saccharomyces cerevisiae MMY011
-
IDH1S92A
-
S98A
Saccharomyces cerevisiae MMY011
-
IDH2S98A
-
V214A
Saccharomyces cerevisiae MMY011
-
residue changes in IDH1 subunits
-
V224A
Saccharomyces cerevisiae MMY011
-
residue changes in IDH1 subunits
-
S102A
-
site-directed mutagenesis, the mutant shows decreased affinity for isocitrate and 3.3% of wild-type activity
S102G
-
site-directed mutagenesis, the mutant shows decreased affinity for isocitrate and 2.8% of wild-type activity
S102T
-
site-directed mutagenesis, the mutant shows decreased affinity for isocitrate and 16% of wild-type activity
S102Y
-
site-directed mutagenesis, the mutant shows decreased affinity for isocitrate and 1.1% of wild-type activity
additional information
-
construction of a knockout mutant of subunit IDH-II, disruption by dissociation insertion element, mutant strain shows normal growth and development, but reduced enzyme activity in mitochondria compared to the wild-type plants, no altered phenotype of the mutant plants, but slightly reduced growth
additional information
P93032, Q8LFC0, Q945K7
characterization of three IDH mutants corresponding to an insertion into a different IDH gene (At5g03290, idhv. At4g35260, idhi. At2g17130, idhii). Analysis of IDH mRNA and protein show that each mutant lacks the corresponding gene products. Leaf IDH activity is reduced by 92%, 60%, and 43% for idhv, idhi, and idhii, respectively; characterization of three IDH mutants corresponding to an insertion into a different IDH gene (At5g03290, idhv. At4g35260, idhi. At2g17130, idhii). Analysis of IDH mRNA and protein show that each mutant lacks the corresponding gene products. Leaf IDH activity is reduced by 92%, 60%, and 43% for idhv, idhi, and idhii, respectively; characterization of three IDH mutants corresponding to an insertion into a different IDH gene (At5g03290, idhv. At4g35260, idhi. At2g17130, idhii). Analysis of IDH mRNA and protein show that each mutant lacks the corresponding gene products. Leaf IDH activity is reduced by 92%, 60%, and 43% for idhv, idhi, and idhii, respectively
additional information
Arabidopsis thaliana Landsberg
-
construction of a knockout mutant of subunit IDH-II, disruption by dissociation insertion element, mutant strain shows normal growth and development, but reduced enzyme activity in mitochondria compared to the wild-type plants, no altered phenotype of the mutant plants, but slightly reduced growth
-
L98P
O43837
the mutation is associated with retinitis pigmentosa
additional information
-
mutational analysis of IDH1 codon 132 in 1185 cancer samples, overview
V225A
Saccharomyces cerevisiae MMY011
-
residue changes in IDH2 subunits
-
additional information
-
transgenic tomato plants expressing the IDH gene in antisense orientation display a mild reduction in the activity of the target enzyme in the leaves but essentially no visible alteration in growth from the wild-type. Fruit size and yield are, however, reduced
Renatured/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
using N-lauroylsarcosine to 0.3% v/v
-