Information on EC 4.2.1.3 - aconitate hydratase

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

EC NUMBER
COMMENTARY
4.2.1.3
-
RECOMMENDED NAME
GeneOntology No.
aconitate hydratase
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
Citrate = cis-aconitate + H2O
show the reaction diagram
-
-
-
-
REACTION TYPE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
elimination
-
-
-
-
PATHWAY
KEGG Link
MetaCyc Link
Biosynthesis of secondary metabolites
-
Carbon fixation pathways in prokaryotes
-
Citrate cycle (TCA cycle)
-
Glyoxylate and dicarboxylate metabolism
-
Metabolic pathways
-
Microbial metabolism in diverse environments
-
SYSTEMATIC NAME
IUBMB Comments
citrate(isocitrate) hydro-lyase (cis-aconitate-forming)
Besides interconverting citrate and cis-aconitate, it also interconverts cis-aconitate with isocitrate and, hence, interconverts citrate and isocitrate. The equilibrium mixture is 91% citrate, 6% isocitrate and 3% aconitate. cis-Aconitate is used to designate the isomer (Z)-prop-1-ene-1,2,3-tricarboxylate. An iron-sulfur protein, containing a [4Fe-4S] cluster to which the substrate binds.
SYNONYMS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
AcnB
P36683
-
AcnB
Escherichia coli W3350
P36683
-
-
ACO
Paracoccidioides brasiliensis ATCC MYA 826
-
-
-
Aco1
D3GQL0
-
Aco1
P21399
cytosolic aconitase
Aco1
Saccharomyces cerevisiae BY4741, Saccharomyces cerevisiae MMY011
-
-
-
Aco2
D3GQL2
-
Aco2
Q99798
mitochondrial aconitase
Aco2
Q9ER34
-
Aco3
D3GQL1
-
aconitase
-
-
-
-
aconitase
-
-
aconitase
Bacillus subtilis NK1010
-
-
-
aconitase
P25516, P36683
-
aconitase
P21399
-
aconitase
Q99798
-
aconitase
-, P28271
-
aconitase
Paracoccidioides brasiliensis ATCC MYA 826
-
-
-
aconitase
Q63270
-
aconitase
Q9ER34
-
aconitase
Saccharomyces cerevisiae BY4741, Saccharomyces cerevisiae MMY011
-
-
-
aconitase
-
-
aconitase
-
-
aconitase 2
Q9ER34
-
aconitase B
-
-
aconitase B
P36683
-
aconitase B
Escherichia coli W3350
P36683
-
-
Aconitate hydratase
-
-
-
-
Aconitate hydratase
B3TZE0
bifunctional enzyme: aconitate hydratase 2/2-methylisocitrate dehydratase
Aconitate hydratase
Advenella kashmirensis DPN7T
B3TZE0
bifunctional enzyme: aconitate hydratase 2/2-methylisocitrate dehydratase
-
Aconitate hydratase
-, P21399
-
Aconitate hydratase
-, P28271
-
Aconitate hydratase
-
-
Aconitate hydratase
Q63270
-
c-acon
-
-
c-aconitase
-
-
cis-aconitase
-
-
-
-
citrate hydro-lyase
-
-
-
-
cytoplasmic aconitase
-
-
cytoplasmic aconitase/iron regulatory protein 1 homolog
-
-
Ferritin repressor protein
-
-
-
-
hydratase, aconitate
-
-
-
-
IP210
-
-
-
-
IRE-BP
-
-
-
-
Iron regulatory protein
-
-
-
-
iron regulatory protein 1
-
-
iron regulatory protein 1
-
-
iron regulatory-like protein
-
-
iron-regulatory protein 1
-
-
iron-responsive element binding protein
-
-
-
-
IRP
-
-
-
-
IRP-1
-
-
IRP1
-
-
-
-
IRP1
P21399
-
IRP1
P28271
-
IRP1
Q63270
-
mACON
-
-
Major iron-containing protein
-
-
-
-
MICP
-
-
-
-
additional information
-
AcnB is a member of the aconitase family
CAS REGISTRY NUMBER
COMMENTARY
9024-25-3
-
ORGANISM
COMMENTARY
LITERATURE
SEQUENCE CODE
SEQUENCE DB
SOURCE
strain DPN7T (DSM 17166T, LMG 22922T)
TrEMBL
Manually annotated by BRENDA team
Advenella kashmirensis DPN7T
strain DPN7T (DSM 17166T, LMG 22922T)
TrEMBL
Manually annotated by BRENDA team
isoforms Aco1, Aco2, Aco3. Cytosolic aconitase is not converted into an iron-responsive element and does not regulate iron homeostasis
-
-
Manually annotated by BRENDA team
isoform aconitase A
-
-
Manually annotated by BRENDA team
early aconitase (isoenzyme I) is present in a culture of 5 h age, late aconitase (isoenzyme II) is present in 12 h age
-
-
Manually annotated by BRENDA team
early aconitase (isoenzyme I) is present in a culture of 5 h age, late aconitase (isoenzyme II) is present in 12 h age; T
-
-
Manually annotated by BRENDA team
Bacillus cereus T
T
-
-
Manually annotated by BRENDA team
bifunctional protein, with aconitase activity and RNA binding activity
-
-
Manually annotated by BRENDA team
gene citB
-
-
Manually annotated by BRENDA team
Bacillus subtilis NK1010
gene citB
-
-
Manually annotated by BRENDA team
strain TM4000
SwissProt
Manually annotated by BRENDA team
isoform aconitase 2
-
-
Manually annotated by BRENDA team
isozyme CcAco1; isozyme CcAco1
UniProt
Manually annotated by BRENDA team
isozyme CcAco2; isozyme CcAco2
UniProt
Manually annotated by BRENDA team
isozyme CcAco3; isozyme CcAco3
UniProt
Manually annotated by BRENDA team
Corynebacterium glutamicum D-248
strain D-248
-
-
Manually annotated by BRENDA team
Cucurbita sp.
3 isoforms: Aco I, Aco II and Aco III
-
-
Manually annotated by BRENDA team
isoforms IRP-1A, the isoform shows aconitase activity, and additionally binds to iron-responsive elements
SwissProt
Manually annotated by BRENDA team
isoforms IRP-1B, the isoform shows aconitase activity, but does not bind to iron-responsive elements
Q9NFX2
SwissProt
Manually annotated by BRENDA team
AcnA; gene AcnA
UniProt
Manually annotated by BRENDA team
AcnB; gene AcnB
SwissProt
Manually annotated by BRENDA team
aconitase A, aconitase B and aconitase C
-
-
Manually annotated by BRENDA team
K 12 strain JRG2387, enzyme form Acn A
-
-
Manually annotated by BRENDA team
strain JRG2387 and JRG3171, contains two major aconitases, AcnA and AcnB
-
-
Manually annotated by BRENDA team
strain W3350
SwissProt
Manually annotated by BRENDA team
Escherichia coli JRG2387
strain JRG2387 and JRG3171, contains two major aconitases, AcnA and AcnB
-
-
Manually annotated by BRENDA team
Escherichia coli W3350
strain W3350
SwissProt
Manually annotated by BRENDA team
bifunctional iron regulatory protein and cytosolic acontiatse
UniProt
Manually annotated by BRENDA team
IRP1
UniProt
Manually annotated by BRENDA team
bifunctional enzyme with aconitase activity and working as iron-responsive protein. Since iron is required for aconitase activity, but inhibits the RNA-binding activity, the two activities are mutually exclusive
-
-
Manually annotated by BRENDA team
isolate Pb01, gene Pbaco
-
-
Manually annotated by BRENDA team
Paracoccidioides brasiliensis ATCC MYA 826
isolate Pb01, gene Pbaco
-
-
Manually annotated by BRENDA team
mutant PAC514 from strain 8602
-
-
Manually annotated by BRENDA team
3 aconitases
-
-
Manually annotated by BRENDA team
aconitase 2; Wistar rats, aconitase 2 encoded by gene Aco2
UniProt
Manually annotated by BRENDA team
Sprague-Dawley rats
-
-
Manually annotated by BRENDA team
strain Male Fischer 344
UniProt
Manually annotated by BRENDA team
strain Sprague-Dawley
-
-
Manually annotated by BRENDA team
Rattus norvegicus Male Fischer 344
strain Male Fischer 344
UniProt
Manually annotated by BRENDA team
Rattus norvegicus Sprague-Dawley
strain Sprague-Dawley
-
-
Manually annotated by BRENDA team
Rheum sp.
i.e. rhubarb
-
-
Manually annotated by BRENDA team
strain MMY011, gene aco1
-
-
Manually annotated by BRENDA team
Saccharomyces cerevisiae MMY011
strain MMY011, gene aco1
-
-
Manually annotated by BRENDA team
Saccharomycopsis lipolytica
-
-
-
Manually annotated by BRENDA team
IFO 12371
-
-
Manually annotated by BRENDA team
Streptomyces viridochromogenes strain Tu494
strain Tu494
-
-
Manually annotated by BRENDA team
IFO 4923
-
-
Manually annotated by BRENDA team
3'-untranslated region; fragment
SwissProt
Manually annotated by BRENDA team
fragment
SwissProt
Manually annotated by BRENDA team
several strains, gene ACO1
-
-
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
malfunction
-
acnA mutants grow very poorly, have secondary mutations, and are quickly outgrown by pseudorevertants. The acnA gene is stably interrupted in a citrate synthase (gltA) null background, indicating that the intracellular accumulation of citrate may be deleterious for survival. No aconitase activity is detected in this mutant. To uncover a function of AcnA beyond its catalytic role in the tricarboxylic acid cycle pathway, the citrate synthase/aconitase (acnA) double mutant is compared with the citrate synthase single mutant. No differences are found
metabolism
-
ACO is an enzyme that catalyzes the isomerization of citrate to isocitrate in both the Krebs cycle and the glyoxylate cycle
metabolism
Paracoccidioides brasiliensis ATCC MYA 826
-
ACO is an enzyme that catalyzes the isomerization of citrate to isocitrate in both the Krebs cycle and the glyoxylate cycle
-
physiological function
P21399, Q99798
iron restriction suppresses mitochondrial and cytosolic aconitase activity in erythroid but not granulocytic or megakaryocytic progenitors. The mechanism for aconitase regulation of erythropoiesis most likely involves both production of metabolic intermediates as well as modulation of erythropoietin signaling; iron restriction suppresses mitochondrial and cytosolic aconitase activity in erythroid but not granulocytic or megakaryocytic progenitors. The mechanism for aconitase regulation of erythropoiesis most likely involves both production of metabolic intermediates as well as modulation of erythropoietin signaling
physiological function
-
aconitase is destabilized in the absence of the Fe4S4 cluster. Apo-form has higher surface hydrophobicity than the holo-form. The lower ground state stability and higher solvent exposed hydrophobic surface of the apo-form makes it aggregation prone. Binding of apo-aconitase to GroEL (molecular chaperone) not only rescues it from the aggregation, but also assists in the final stage of maturation by orienting the cluster insertion site of GroEL bound apo-protein
physiological function
Q9ER34
it is investigated if oxidative inactivation of mitochondrial aconitase results in the release of redox-active iron and hydrogen peroxide and whether this contributes to cell death. Using an adenoviral construct mitochondrial aconitase is over-expressed in primary mesencephalic cultures. Oxidative inactivation of m-aconitase over-expressing cultures results in exacerbation of H2O2 production, Fe2+ accumulation and increased neuronal death. Increased cell death in m-aconitase overexpressing cultures is attenuated by addition of catalase and/or a cell permeable iron chelator suggesting that neuronal death occurred in part via astrocyte-derived H2O2
physiological function
-
aconitase is a bifunctional enzyme, which can not only interconvert citrate and isocitrate, but also has the RNA binding function similar to the eukaryotic protein IRP-1, iron regulatory protein 1
physiological function
-
the increase in citrate, caused by aconitase inhibition, induces amino acid synthesis and the gamma-aminobutyrate shunt, in accordance with the suggested fate of citrate during the acid decline stage in citrus fruit
physiological function
Bacillus subtilis NK1010
-
aconitase is a bifunctional enzyme, which can not only interconvert citrate and isocitrate, but also has the RNA binding function similar to the eukaryotic protein IRP-1, iron regulatory protein 1
-
SUBSTRATE
PRODUCT                      
REACTION DIAGRAM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
(2R,3S)-2-methylisocitrate
(Z)-2-methylaconitate + H2O
show the reaction diagram
Escherichia coli, Escherichia coli W3350
P36683
enzyme is involved in pathway of oxidation of propionate to pyruvate
-
?
(Z)-2-methylaconitate + H2O
(2R,3S)-2-methylisocitrate
show the reaction diagram
Escherichia coli, Escherichia coli W3350
P36683
enzyme is involved in pathway of oxidation of propionate to pyruvate
-
r
alpha-methyl-cis-aconitate
alpha-methylisocitrate
show the reaction diagram
Bos taurus, Saccharomycopsis lipolytica
-
-
-
?
cis-aconitate
citrate
show the reaction diagram
-
-
-
r
cis-aconitate
isocitrate
show the reaction diagram
-
-
-
-
cis-aconitate
isocitrate
show the reaction diagram
-
-
-
-
cis-aconitate
isocitrate
show the reaction diagram
-
-
-
r
cis-aconitate
isocitrate
show the reaction diagram
-
-
-
-
cis-aconitate
isocitrate
show the reaction diagram
-
-
-
r
cis-aconitate + H2O
?
show the reaction diagram
Escherichia coli, Escherichia coli JRG2387
-
-
-
?
cis-aconitate + H2O
citrate
show the reaction diagram
-
-
-
-
?
cis-aconitate + H2O
citrate
show the reaction diagram
-
-
-
?
cis-aconitate + H2O
isocitrate
show the reaction diagram
-
-
-
-
?
cis-aconitate + H2O
isocitrate
show the reaction diagram
-
-
-
-
?
cis-aconitate + H2O
isocitrate
show the reaction diagram
-
-
-
-
?
cis-aconitate + H2O
isocitrate
show the reaction diagram
P25516, P36683
-
-
-
r
cis-aconitate + H2O
isocitrate
show the reaction diagram
Q9NFX2, Q9NFX3
-
-
-
?
cis-aconitate + H2O
isocitrate
show the reaction diagram
P25516, P36683
aconitase catalyzes a reversible isomerization of citrate into isocitrate in the Krebs cycle
-
-
r
citrate
cis-aconitate
show the reaction diagram
-
-
-
-
citrate
cis-aconitate
show the reaction diagram
-
-
-
?
citrate
cis-aconitate
show the reaction diagram
-
-
-
-
citrate
cis-aconitate
show the reaction diagram
-
-
-
r
citrate
cis-aconitate
show the reaction diagram
-
-
-
-
citrate
cis-aconitate
show the reaction diagram
-
-
-
-
citrate
cis-aconitate
show the reaction diagram
-
-
-
r
citrate
isocitrate
show the reaction diagram
-
-
-
-
?
citrate
isocitrate
show the reaction diagram
-
-
-
-
r
citrate
isocitrate
show the reaction diagram
-
-
-
-
-
citrate
isocitrate
show the reaction diagram
-
-
-
-
?
citrate
isocitrate
show the reaction diagram
-
-
-
r
citrate
isocitrate
show the reaction diagram
-
-
-
-
-
citrate
isocitrate
show the reaction diagram
-
-
-
-
citrate
isocitrate
show the reaction diagram
-
-
-
r
citrate
isocitrate
show the reaction diagram
-
-
-
-
?
citrate
isocitrate
show the reaction diagram
-
-
-
r
citrate
isocitrate
show the reaction diagram
Saccharomycopsis lipolytica
-
-
-
-
?
citrate
isocitrate
show the reaction diagram
Bacillus cereus T
-
-
-
-
?
citrate
cis-aconitate + H2O
show the reaction diagram
-
-
-
?
citrate
cis-aconitate + H2O
show the reaction diagram
-
-
-
-
?
citrate
cis-aconitate + H2O
show the reaction diagram
-
-
-
-
?
citrate
cis-aconitate + H2O
show the reaction diagram
-
-
-
-
?
citrate
cis-aconitate + H2O
show the reaction diagram
-
-
-
-
?
citrate
cis-aconitate + H2O
show the reaction diagram
-
-
-
-
r
citrate
cis-aconitate + H2O
show the reaction diagram
-
-
-
-
?
citrate
cis-aconitate + H2O
show the reaction diagram
P25516, P36683
-
-
-
r
citrate
cis-aconitate + H2O
show the reaction diagram
P25516, P36683
aconitase catalyzes a reversible isomerization of citrate into isocitrate in the Krebs cycle
-
-
r
citrate
cis-aconitate + H2O
show the reaction diagram
Paracoccidioides brasiliensis ATCC MYA 826
-
-
-
-
?
citrate
cis-aconitate + H2O
show the reaction diagram
-
-
-
-
r
citrate
cis-aconitate + H2O
show the reaction diagram
Escherichia coli JRG2387
-
-
-
?
isocitrate
citrate
show the reaction diagram
-
-
-
-
-
isocitrate
citrate
show the reaction diagram
-
-
-
-
?
isocitrate
citrate
show the reaction diagram
-
-
-
r
isocitrate
citrate
show the reaction diagram
-
-
-
-
-
isocitrate
citrate
show the reaction diagram
-
-
-
r
isocitrate
citrate
show the reaction diagram
-
-
-
-
?
isocitrate
citrate
show the reaction diagram
-
-
-
r
isocitrate
citrate
show the reaction diagram
Saccharomycopsis lipolytica
-
-
-
-
?
isocitrate
citrate
show the reaction diagram
Bacillus cereus T
-
-
-
-
?
isocitrate
cis-aconitate
show the reaction diagram
-
-
-
?
isocitrate
cis-aconitate
show the reaction diagram
-
-
-
?
isocitrate
cis-aconitate
show the reaction diagram
-
-
-
r
isocitrate
cis-aconitate
show the reaction diagram
-
-
-
-
isocitrate
cis-aconitate
show the reaction diagram
-
-
-
r
isocitrate
cis-aconitate
show the reaction diagram
-
-
-
?
isocitrate
cis-aconitate
show the reaction diagram
-
-
-
-
?
isocitrate
cis-aconitate
show the reaction diagram
-
-
-
?
isocitrate
cis-aconitate + H2O
show the reaction diagram
-
-
-
-
?
isocitrate
cis-aconitate + H2O
show the reaction diagram
-
-
-
?
isocitrate
cis-aconitate + H2O
show the reaction diagram
-
-
-
-
r
isocitrate
cis-aconitate + H2O
show the reaction diagram
-
-
-
-
?
isocitrate
cis-aconitate + H2O
show the reaction diagram
-
-
-
-
r
isocitrate
cis-aconitate + H2O
show the reaction diagram
-
-
-
-
?
isocitrate
cis-aconitate + H2O
show the reaction diagram
-
-
-
-
r
isocitrate
cis-aconitate + H2O
show the reaction diagram
Escherichia coli JRG2387
-
-
-
?
isocitrate
?
show the reaction diagram
-
-
-
?
threo-D-alpha-methylisocitrate
?
show the reaction diagram
Saccharomycopsis lipolytica
-
-
-
-
?
isocitrate
?
show the reaction diagram
Q9NJQ8, Q9NJQ9, -
-
-
?
additional information
?
-
P36683
no detectable activity with (2S,3S)-methylcitrate
-
?
additional information
?
-
P16276
the mechanism requires that the intermediate product cis-aconitate, flip over by 180° about the Calpha-Cbeta double bond
-
?
additional information
?
-
-
one or more of the aconitases may contribute to the control of the synthesis of the virulence factor exotoxin A
-
-
-
additional information
?
-
-
Mn2+ exposure leads to a region-specific alteration in total aconitase: 48.5% reduction of the enzyme activity in frontal cortex, 33.7% in striatum and 20.6% in substantia nigra. This leads to the disruption of mitochondrial energy production and cellular Fe metabolism in the brain
-
-
-
additional information
?
-
-
inductively formed in presence of fluorocitrate
-
-
-
additional information
?
-
-
aconitase B is the major isoenzyme which is synthesized earlier in the growth cycle than aconitase A and is subject to catabolite and anaerobic repression
-
-
-
additional information
?
-
-
inductively formed in presence of fluoroacetate
-
-
-
additional information
?
-
Cucurbita sp.
-
enzyme is involved in the glyoxylate cycle
-
-
-
additional information
?
-
-
iron-responsive element binding protein is required in the posttranscriptional regulation of ferritin mRNA translation and stabilization of transferrin receptor mRNA
-
-
-
additional information
?
-
-
2fold increase in mitochondrial cis-aconitase activity in UVA-exposed cells coincides with the time of maximal heme oxygenase-1 expression. Modulation of cis-aconitase activity at the translational level by an increase of cellular iron is an important consequence of heme oxygenase-1 activation
-
?
additional information
?
-
-, Q8RP87
Bacteroides fragilis has two separate pathways to generate alpha-ketoglutarate, either of which is sufficient for growth, a heme-dependent pathway and a heme-independent pathway. Aconitase is involved in the heme-independent pathway
-
?
additional information
?
-
-
bifunctional protein, showing aconitase activity in presence of iron and RNA binding activity when cells are iron-deprived
-
?
additional information
?
-
-
C1 aconitase is constitutive of the glyoxylate cycle. In addition, the same isoform is found to be active during pathogenic attack as well, hypocotyls. It might by assumed that in such a case the glyoxylate cycle is reinitiated as a part of a carbon reallocation system feeding on the diseased tissue cellular components
-
?
additional information
?
-
-
inactivation of the tricarboxylic acid cycle aconitase gene impairs the morphological and physiological differentiation of Streptomyces viridochromogenes Tue949, which produces the herbicide phosphinothricin tripeptide
-
?
additional information
?
-
-
iron regulatory protein-1 controls the expression of several mRNAs by binding to iron-responsive elements in their untranslated regions. In iron-replete cells, a 4Fe-4S cluster converts IRP-1 to cytoplasmic aconitase. Iron regulatory protein activity is restored by cluster loss in response to iron starvation, NO, or extracellular H2O2
-
?
additional information
?
-
Q9NJQ8, Q9NJQ9, -
the enzyme does not take part in the mitochondrial Krebs cycle but may have a yet unknown function in the cytoplasm of the parasite
-
?
additional information
?
-
P36683
the HEAT-like domain, implies a role in protein-protein recognition
-
?
additional information
?
-
-
aconitase B is the major citric acid cycle aconitase and also a post-transcriptional regulator
-
-
-
additional information
?
-
-
aconitase is part of a multienzyme complex of the tricarboxylic acid cycle. Individual enzyme activities of fumarase, malate dehydrogenase, citrate synthase, aconitase and isocitrate dehydrogenase can be used to reconstitute the complex
-
-
-
additional information
?
-
-
in cytosol the enzyme participates in the glyoxylate shunt, in mitochondria the enzyme participates in the tricarboxylic acid cycle
-
-
-
additional information
?
-
-
IRP1 functions as a cytoplasmic aconitase. It may provide a link between citrate and iron metabolism and may be involved in oxidative stress response
-
-
-
additional information
?
-
-
key enzyme for citrate oxidation in the epithelial cell of the human prostate. Hemin and ferric ammonium citrate increase activity and gene expression
-
-
-
additional information
?
-
-
the enzyme is involved in the assimilation of Fe and excess dietary Zn can result in negative interactions
-
-
-
additional information
?
-
-
toxic hepatitis is accompanied by inactivation of aconitate hydratase. Inhibition of the enzyme probably contributes to intracellular accumulation of citrate and inhibition of the Fenton reaction
-
-
-
additional information
?
-
-
additionally to catalytic activity, enzyme is able to bind specifically the 5’ UTP of the Arabidopsis chloroplastic CuZn superoxide dismutase 2 mRNA. Enzyme does not bind an iron responsive element of the human ferritin gene
-
-
-
additional information
?
-
-
enzyme binds to both ds- and ssDNA, with a preference for GC-containing sequences. It protects mitochondrial DNA from excessive accumulation of point mutations and ssDNA breaks and suppresses reductive recombination of mitochondrial DNA
-
-
-
additional information
?
-
-
in addition to aconitase activity, enzyme binds with high specificity to iron-responsive element-like RNA sequences. Iron is required for aconitase activity, but inhibits the RNA-binding activity, the two activities are mutually exclusive
-
-
-
additional information
?
-
Q9NFX2, Q9NFX3
isoform IRP-1A binds in vitro both Drosophila ferritin iron-responsive element and human ferritin iron-responsive element in the presence of a reducing agent
-
-
-
additional information
?
-
-
cytoplasmic aconitase/iron regulatory protein 1 homolog is up-regulated in the pulvinus bundle sheath cells after gravistimulation in presence of H2O2 and ascorbic acid, overview. Reactive oxygen species levels increase rapidly in gravistimulated maize pulvini
-
-
-
additional information
?
-
-
effects of lipoic acid on intensity of free radical reactions, citrate content, and aconitate hydratase during myocardial ischemia, overview
-
-
-
additional information
?
-
-
impairing aconitase activity precedes decreased cell proliferation
-
-
-
additional information
?
-
Q9ER34
regulation of mitochondrial aconitase activity by protein kinase C-dependent phosphorylation, augmented phosphorylation of mitochondrial aconitase in diabetic hearts is associated with an increase in its reverse activity, converting isocitrate to aconitate, while the rate of the forward activity is unchanged, overview
-
-
-
additional information
?
-
Q63270
role of aconitate hydratase and structurally similar iron-regulatory protein in maintenance of homeostasis of cell iron, overview. Decrease in enzyme activity and increase in citrate content in the tissues of mammals under hypoxia, ischemia, hyperoxia, and CCl4-induced hepatitis. Regulation, overview, role of aconitate hydratase and structurally similar iron-regulatory protein in maintenance of homeostasis of cell iron, overview. IRP2 dominates in the regulation of iron metabolism in mammals. Decrease in enzyme activity and increase in citrate content in the tissues of mammals under hypoxia, ischemia, hyperoxia, and CCl4-induced hepatitis. Regulation, overview
-
-
-
additional information
?
-
P28271
role of aconitate hydratase and structurally similar iron-regulatory protein in maintenance of homeostasis of cell iron, overview. Regulation, overview
-
-
-
additional information
?
-
P21399
role of aconitate hydratase and structurally similar iron-regulatory protein in maintenance of homeostasis of cell iron, overview. The enzyme may be involved also in regulation of individual enzyme activities. Blocking of isozyme mAH expression and activity by 40-60% causes a decrease in ATP biosynthesis, increase in citrate secretion, and reduction of the rate of proliferation of human prostate carcinoma cells. extracellular H2O2 strongly induces IRP1 through a signal cascade, introduction of a source of iron ions enhances glutamate secretion in cultivated lens cells and neurons through an increase in cAH activity and intensification of isocitrate formation. The maximal activity requires the presence of sulfhydryl compounds in the medium, role of aconitate hydratase and structurally similar iron-regulatory protein in maintenance of homeostasis of cell iron, overview. The enzyme may be involved also in regulation of individual enzyme activities. Decrease in enzyme activity and increase in citrate content in the tissues of mammals under hypoxia, ischemia, hyperoxia, and CCl4-induced hepatitis. A decrease in enzyme activity is observed in some neurodegenerative diseases associated with the development of oxidative stress, in particular, Parkinson’s and Alzheimer’s diseases. Regulation, overview. Extracellular H2O2 strongly induces IRP1 through a signal cascade
-
-
-
additional information
?
-
-
weak interactions, which affects structure and function of the proteins, of aconitase B and isocitrate dehydrogenase, overview. Two monomeric AcnB regions associate with the homodimeric ICDH region. The versatile architecture of AcnB may alter the metabolic process involving the Krebs cycle
-
-
-
additional information
?
-
Q63270
IRP shows RNA-binding activity, which is affected by some hormones and growth factors, e.g. thyroid, erythropoietin, and epidermal growth factor
-
-
-
additional information
?
-
-
the active sites within ICDH-AcnB catalyze the three consecutive reactions, in which citrate is converted to 2-oxoglutarate, via cisaconitate and isocitrate
-
-
-
additional information
?
-
P25516, P36683
the substrate binding may induce a rearrangement of their relative positions. Such a conformational change may result in the negative cooperativity
-
-
-
additional information
?
-
-
it is demonstrated that the extramitochondrial form of frataxin directly interacts with cytosolic aconitase/iron regulatory protein-1 (IRP1). The inability to produce normal levels of the mitochondrial protein frataxin causes the hereditary degenerative disorder Friedreich’s Ataxia (FRDA)
-
-
-
additional information
?
-
-
amino acid residues Arg741 and Gln745 play great role in the aconitase function
-
-
-
additional information
?
-
Escherichia coli W3350
P36683
no detectable activity with (2S,3S)-methylcitrate
-
?
additional information
?
-
Bacillus subtilis NK1010
-
amino acid residues Arg741 and Gln745 play great role in the aconitase function
-
-
-
additional information
?
-
Streptomyces viridochromogenes strain Tu494
-
inactivation of the tricarboxylic acid cycle aconitase gene impairs the morphological and physiological differentiation of Streptomyces viridochromogenes Tue949, which produces the herbicide phosphinothricin tripeptide
-
?
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
(Z)-2-methylaconitate + H2O
(2R,3S)-2-methylisocitrate
show the reaction diagram
Escherichia coli, Escherichia coli W3350
P36683
enzyme is involved in pathway of oxidation of propionate to pyruvate
-
r
cis-aconitate + H2O
isocitrate
show the reaction diagram
-
-
-
-
?
cis-aconitate + H2O
isocitrate
show the reaction diagram
-
-
-
-
?
cis-aconitate + H2O
isocitrate
show the reaction diagram
P25516, P36683
aconitase catalyzes a reversible isomerization of citrate into isocitrate in the Krebs cycle
-
-
r
citrate
cis-aconitate + H2O
show the reaction diagram
-
-
-
-
?
citrate
cis-aconitate + H2O
show the reaction diagram
-
-
-
-
?
citrate
cis-aconitate + H2O
show the reaction diagram
-
-
-
-
r
citrate
cis-aconitate + H2O
show the reaction diagram
-
-
-
-
?
citrate
cis-aconitate + H2O
show the reaction diagram
P25516, P36683
aconitase catalyzes a reversible isomerization of citrate into isocitrate in the Krebs cycle
-
-
r
citrate
cis-aconitate + H2O
show the reaction diagram
Paracoccidioides brasiliensis ATCC MYA 826
-
-
-
-
?
citrate
cis-aconitate + H2O
show the reaction diagram
-
-
-
-
r
additional information
?
-
-
one or more of the aconitases may contribute to the control of the synthesis of the virulence factor exotoxin A
-
-
-
additional information
?
-
-
Mn2+ exposure leads to a region-specific alteration in total aconitase: 48.5% reduction of the enzyme activity in frontal cortex, 33.7% in striatum and 20.6% in substantia nigra. This leads to the disruption of mitochondrial energy production and cellular Fe metabolism in the brain
-
-
-
additional information
?
-
-
inductively formed in presence of fluorocitrate
-
-
-
additional information
?
-
-
aconitase B is the major isoenzyme which is synthesized earlier in the growth cycle than aconitase A and is subject to catabolite and anaerobic repression
-
-
-
additional information
?
-
-
inductively formed in presence of fluoroacetate
-
-
-
additional information
?
-
Cucurbita sp.
-
enzyme is involved in the glyoxylate cycle
-
-
-
additional information
?
-
-
iron-responsive element binding protein is required in the posttranscriptional regulation of ferritin mRNA translation and stabilization of transferrin receptor mRNA
-
-
-
additional information
?
-
-
2fold increase in mitochondrial cis-aconitase activity in UVA-exposed cells coincides with the time of maximal heme oxygenase-1 expression. Modulation of cis-aconitase activity at the translational level by an increase of cellular iron is an important consequence of heme oxygenase-1 activation
-
?
additional information
?
-
-, Q8RP87
Bacteroides fragilis has two separate pathways to generate alpha-ketoglutarate, either of which is sufficient for growth, a heme-dependent pathway and a heme-independent pathway. Aconitase is involved in the heme-independent pathway
-
?
additional information
?
-
-
bifunctional protein, showing aconitase activity in presence of iron and RNA binding activity when cells are iron-deprived
-
?
additional information
?
-
-
C1 aconitase is constitutive of the glyoxylate cycle. In addition, the same isoform is found to be active during pathogenic attack as well, hypocotyls. It might by assumed that in such a case the glyoxylate cycle is reinitiated as a part of a carbon reallocation system feeding on the diseased tissue cellular components
-
?
additional information
?
-
-
inactivation of the tricarboxylic acid cycle aconitase gene impairs the morphological and physiological differentiation of Streptomyces viridochromogenes Tue949, which produces the herbicide phosphinothricin tripeptide
-
?
additional information
?
-
-
iron regulatory protein-1 controls the expression of several mRNAs by binding to iron-responsive elements in their untranslated regions. In iron-replete cells, a 4Fe-4S cluster converts IRP-1 to cytoplasmic aconitase. Iron regulatory protein activity is restored by cluster loss in response to iron starvation, NO, or extracellular H2O2
-
?
additional information
?
-
Q9NJQ8, Q9NJQ9, -
the enzyme does not take part in the mitochondrial Krebs cycle but may have a yet unknown function in the cytoplasm of the parasite
-
?
additional information
?
-
P36683
the HEAT-like domain, implies a role in protein-protein recognition
-
?
additional information
?
-
-
aconitase B is the major citric acid cycle aconitase and also a post-transcriptional regulator
-
-
-
additional information
?
-
-
aconitase is part of a multienzyme complex of the tricarboxylic acid cycle. Individual enzyme activities of fumarase, malate dehydrogenase, citrate synthase, aconitase and isocitrate dehydrogenase can be used to reconstitute the complex
-
-
-
additional information
?
-
-
in cytosol the enzyme participates in the glyoxylate shunt, in mitochondria the enzyme participates in the tricarboxylic acid cycle
-
-
-
additional information
?
-
-
IRP1 functions as a cytoplasmic aconitase. It may provide a link between citrate and iron metabolism and may be involved in oxidative stress response
-
-
-
additional information
?
-
-
key enzyme for citrate oxidation in the epithelial cell of the human prostate. Hemin and ferric ammonium citrate increase activity and gene expression
-
-
-
additional information
?
-
-
the enzyme is involved in the assimilation of Fe and excess dietary Zn can result in negative interactions
-
-
-
additional information
?
-
-
toxic hepatitis is accompanied by inactivation of aconitate hydratase. Inhibition of the enzyme probably contributes to intracellular accumulation of citrate and inhibition of the Fenton reaction
-
-
-
additional information
?
-
-
cytoplasmic aconitase/iron regulatory protein 1 homolog is up-regulated in the pulvinus bundle sheath cells after gravistimulation in presence of H2O2 and ascorbic acid, overview. Reactive oxygen species levels increase rapidly in gravistimulated maize pulvini
-
-
-
additional information
?
-
-
effects of lipoic acid on intensity of free radical reactions, citrate content, and aconitate hydratase during myocardial ischemia, overview
-
-
-
additional information
?
-
-
impairing aconitase activity precedes decreased cell proliferation
-
-
-
additional information
?
-
Q9ER34
regulation of mitochondrial aconitase activity by protein kinase C-dependent phosphorylation, augmented phosphorylation of mitochondrial aconitase in diabetic hearts is associated with an increase in its reverse activity, converting isocitrate to aconitate, while the rate of the forward activity is unchanged, overview
-
-
-
additional information
?
-
Q63270
role of aconitate hydratase and structurally similar iron-regulatory protein in maintenance of homeostasis of cell iron, overview. Decrease in enzyme activity and increase in citrate content in the tissues of mammals under hypoxia, ischemia, hyperoxia, and CCl4-induced hepatitis. Regulation, overview, role of aconitate hydratase and structurally similar iron-regulatory protein in maintenance of homeostasis of cell iron, overview. IRP2 dominates in the regulation of iron metabolism in mammals. Decrease in enzyme activity and increase in citrate content in the tissues of mammals under hypoxia, ischemia, hyperoxia, and CCl4-induced hepatitis. Regulation, overview
-
-
-
additional information
?
-
P28271
role of aconitate hydratase and structurally similar iron-regulatory protein in maintenance of homeostasis of cell iron, overview. Regulation, overview
-
-
-
additional information
?
-
P21399
role of aconitate hydratase and structurally similar iron-regulatory protein in maintenance of homeostasis of cell iron, overview. The enzyme may be involved also in regulation of individual enzyme activities. Blocking of isozyme mAH expression and activity by 40-60% causes a decrease in ATP biosynthesis, increase in citrate secretion, and reduction of the rate of proliferation of human prostate carcinoma cells. extracellular H2O2 strongly induces IRP1 through a signal cascade, introduction of a source of iron ions enhances glutamate secretion in cultivated lens cells and neurons through an increase in cAH activity and intensification of isocitrate formation. The maximal activity requires the presence of sulfhydryl compounds in the medium, role of aconitate hydratase and structurally similar iron-regulatory protein in maintenance of homeostasis of cell iron, overview. The enzyme may be involved also in regulation of individual enzyme activities. Decrease in enzyme activity and increase in citrate content in the tissues of mammals under hypoxia, ischemia, hyperoxia, and CCl4-induced hepatitis. A decrease in enzyme activity is observed in some neurodegenerative diseases associated with the development of oxidative stress, in particular, Parkinson’s and Alzheimer’s diseases. Regulation, overview. Extracellular H2O2 strongly induces IRP1 through a signal cascade
-
-
-
additional information
?
-
-
weak interactions, which affects structure and function of the proteins, of aconitase B and isocitrate dehydrogenase, overview. Two monomeric AcnB regions associate with the homodimeric ICDH region. The versatile architecture of AcnB may alter the metabolic process involving the Krebs cycle
-
-
-
additional information
?
-
-
it is demonstrated that the extramitochondrial form of frataxin directly interacts with cytosolic aconitase/iron regulatory protein-1 (IRP1). The inability to produce normal levels of the mitochondrial protein frataxin causes the hereditary degenerative disorder Friedreich’s Ataxia (FRDA)
-
-
-
additional information
?
-
Streptomyces viridochromogenes strain Tu494
-
inactivation of the tricarboxylic acid cycle aconitase gene impairs the morphological and physiological differentiation of Streptomyces viridochromogenes Tue949, which produces the herbicide phosphinothricin tripeptide
-
?
COFACTOR
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
thiamine diphosphate
Q9ER34
-
METALS and IONS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
Fe
-
IRP1 binds a [4Fe-4S] cluster
Fe
-
a iron-mediated dimerization mechanism for switching AcnB between its catalytic and regulatory form is proposed
Fe
P21399, Q99798
iron restriction reproducibly causes 60% decreases in both mitochondrial and cytosolic aconitase activities in erythroid samples
Fe2+
-
enzyme activity increases 2-4fold in presence of both Fe2+ and cysteine. 0.1-1 mM Fe2+ and 0.05-0.5 mM cysteine
Fe2+
-
activates the enzyme under normal conditions and in animals with toxic hepatitis. The stimulatory effect of Fe2+ in concentrations below 1 mM is less pronounced than in animals with toxic hepatitis
Fe2+
P25516, P36683
the iron-sulfur cluster, which constitutes the active site, is located at the interdomain boundary among the three enzyme domains, overview; the iron-sulfur cluster, which constitutes the active site, is located at the interdomain boundary among the three enzyme domains, overview
Fe2+
P21399
required; required, both isoenzymes have an [4Fe-4S] iron-sulfur cluster bound with cysteine residues Cys437, Cys503, and Cys506, under the action of reductants, the active enzyme form is produced with a complex cation of the [3Fe–3S]2+ type, structure, and mechanism of activation of the enzyme by Fe2+, overview
Fe2+
P28271
required, binding structure in the [Fe-S] cluster, mechanism of activation of the enzyme by Fe2+, overview
Fe2+
Q63270
required, binding structure in the [4Fe-4S] cluster, mechanism of activation of the enzyme by Fe2+, overview
Fe2+
-
required, the enzyme contains iron-sulfur clusters. Chelating mitochondrial free iron in various cell systems causes loss of aconitase activity
Fe2+
-
mitochondrial aconitase contains iron-sulfur cluster
Fe2+
P21399, Q99798
iron restriction reproducibly causes 60% decreases in both mitochondrial and cytosolic aconitase activities in erythroid samples
Iron
-
contains 2.1 mol of iron per mol of enzyme
Iron
-
crystallographic evidence for a three-iron center
Iron
-
inactive aconitase contains an oxidized [3Fe-4S]+cluster. Full activity is achieved with one electron per 3Fe cluster and at least 0.6 gatoms of Fe2+ per mol. The process involves building up of [4Fe-4S]2+ clusters
Iron
-
inactive aconitase contains a single [3Fe-4S]cluster
Iron
-
iron-sulfur enzyme
Iron
-
contains 2 gatoms of non-heme iron per mol of enzyme
Iron
-
contains 2 gatoms of non-heme iron per mol of enzyme
Iron
-
cytosolic and mitochondrial isoenzyme require an intact [4Fe-4S] cluster. Mitochondrial aconitase is isolated predominantly in the [3Fe-4S] form (Fe/S ratio of 0.73) and must be activated by the addition of Fe2+. The cytoplasmic aconitase as isolated is about 80% active with a Fe/S ratio of 1.1
Iron
-
the active form contains a [4Fe-4S]+ cluster, the inactive form contains a [3Fe-4S]+ cluster
Iron
-
Cys358, Cys421 and Cys424 are ligands to the Fe-S cluster in the inactive [3Fe-4S] form and the active [4Fe-4S] form
Iron
-
a significant proportion of the enzyme is in the inactive [3Fe-4S]1+ or apoenzyme forms. AcnB contains a much higher proportion of inactive enzyme than AcnA
Iron
-
the enzyme contains a [4Fe-4S]2+ cluster
Iron
-
the enzyme hosts an interconvertible [3Fe-4S] cluster
Iron
-
iron regulatory protein-1 controls the expression of several mRNAs by binding to iron-responsive elements in their untranslated regions. In iron-replete cells, a 4Fe-4S cluster converts IRP-1 to cytoplasmic aconitase. Iron regulatory protein activity is restored by cluster loss in response to iron starvation, NO, or extracellular H2O2
Iron
Q23500
activity is posttranslationally regulated by iron
Iron
P16276
in the S642A:citrate complex citrate is directly coordinated to Fe4 of the [4Fe-4S] cluster via Cbeta carboxyl and hydroxyl oxygen atoms
Iron
-
contains a [4Fe-4D] cluster
Iron
-
[4Fe-4S] cluster. The [4Fe-4S] cluster loaded form of the IscU [Fe-S] cluser scaffolding protein can be used for intact cluster transfer to an apo form of aconitase A. IscU mutant D39A is an effective inhibitor of IscU-directed activation of apo-aconitase A
Iron
-
[4Fe-4S] cluster
Iron
-
iron-induced increase in L-glutamate availability increases via the aconitase pathway L-cystine uptake, with subsequent increases in glutathione levels
Iron
-
iron is required for aconitase activity, but inhibits the RNA-binding activity, the two activities are mutually exclusive
Iron
P21399
under iron-replete conditions, enzyme binds a [4Fe-4S] cluster und functions as cytosolic aconitase. Under iron shortage, enzyme is involved in translational control as an iron regulatory protein
Zn
-
an X-ray fluorescence measurement performed on a gold-derivative crystal shows the unexpected presence of zinc, in addition to gold and iron
Mg2+
Q9ER34
-
additional information
Q63270
IRP1 is a cytosolic isozyme devoid of labile Fe2+
INHIBITORS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
1,10-phenanthroline
-
noncompetitive
1,10-phenanthroline
Saccharomycopsis lipolytica
-
-
1,10-phenanthroline
P36683
-
1,2,3,4-tetracarboxycyclopentane
-
competitive
1,2,3-tricarboxycyclopentene-1
-
competitive
1,3,5-tricarboxypentane
-
competitive
2,2'-dipyridyl
-
noncompetitive
4-hydroxy-2-oxoglutarate
-
competitive
Adipate
Saccharomycopsis lipolytica
-
-
ADP
-
inhibition at levels well above its physiological concentration
alpha-picolinic acid
-
noncompetitive
Cd2+
-
exposure of isolated mitochondria to 0.05 mM Cd2+ results in 20-25% inhibition of mitochondrial aconitase activity. Exposure of whole oysters to Cd2+ for 3-6 weeks has no effect on aconitase activity
Cd2+
-
inactivation of enzyme, particularly at elevated temperature
citramalate
D3GQL0, D3GQL1, D3GQL2
a competitive inhibitor of aconitase activity; a competitive inhibitor of aconitase activity; a competitive inhibitor of aconitase activity
citramalate
-
an endogenous compound of fruit pulp, is a competitive endogenous inhibitor of citrus aconitase, it significantly increases citrate content and reduces the mitochondrial isozyme activity, while slightly inducing its protein level
citrate
P21399
citrate accumulation under enzyme inhibition restricts the formation of hydroxyl radical in the Fenton reaction through the binding of iron ions, and it thus protects the enzyme from inactivation
citrate
P28271
citrate accumulation under enzyme inhibition restricts the formation of hydroxyl radical in the Fenton reaction through the binding of iron ions, and it thus protects the enzyme from inactivation
citrate
Q63270
citrate accumulation under enzyme inhibition restricts the formation of hydroxyl radical in the Fenton reaction through the binding of iron ions, and it thus protects the enzyme from inactivation
D-glucose 1-phosphate
-
-
D-glucose 6-phosphate
-
-
deferiprone
-
the loss of aconitase activity observed in cells should be ascribed to the chelation of available iron rather than to a direct effect of the chelator on the iron-sulfur clusters of the enzyme
ethyl picolinate
-
isoenzyme is inhibited, isoenzyme I is less or not sensitive
fluoroacetate
Saccharomycopsis lipolytica
-
-
Fluorocitrate
-
-
Fluorocitrate
-
linear competitive
Fluorocitrate
-
-
Fluorocitrate
-
mechanism-based inhibitor
Fluorocitrate
Cucurbita sp.
-
competitive
Fluorocitrate
P21399, Q99798
active site aconitase inhibitor blocks erythroid differentiation in a manner similar to iron deprivation; active site aconitase inhibitor blocks erythroid differentiation in a manner similar to iron deprivation
fructose-6-phosphate
P21399
-
fructose-6-phosphate
P28271
-
fructose-6-phosphate
Q63270
;
GDP
-
inhibition at levels well above its physiological concentration
glyoxylate
-
-
H2O2
-
H2O2 does not exert its inhibitory effects by acting directly on the enzyme, rather inactivation appears to result from interactions between aconitase and a mitochondrial membrane component responsive to H2O2. Prolonged exposure of mitochondria to steady-state levels of H2O2 or O2- results in disassembly of the [4Fe-4S]2+ cluster, carbonylation, and protein degradation
H2O2
-
2.3 mM, 90-95% inhibition
hydrogen peroxide
-
inhibits enzyme activity in cell-free extracts
Indomethacin
-
a non-steroidal anti-inflammatory drug, carbonylation of aconitase and release of iron along with the loss of activity in vivo after indomethacin treatment, activation of mitochondrial death pathway by indomethacin, overview
Maleate
Saccharomycopsis lipolytica
-
-
-
nitric oxide
-
brief exposure leads to a reversible inhibition competitive with isocitrate. subsequently, an irreversible inactivation is observed
nitrosoglutathione
-
irreversible inactivation both in presence and absence of substrate
oxaloacetate
-
parabolic noncompetitive
oxaloacetate
-
-
Oxalomalate
P21399
inhibition of the enzyme by oxalomalate reduces glutamate secretion and eliminates the effect of iron ions on the latter
Oxalomalate
-
significantly increases citrate content and reduces the enzyme's activity, while slightly inducing its protein level. Specific activities of amino acid-metabolizing enzymes are induced in oxalomalate-treated callus cells, overview
oxalomalic acid
-
inhibition of aconitase activity, leading to inhibition of L-glutamate production, L-cystine uptake, and decrease in glutathione concentration in lens epithelial cells and retinal pigment epithelial cells
oxalosuccinate
P21399
-
-
oxalosuccinate
P28271
-
-
oxalosuccinate
Q63270
;
-
p-hydroxymercuribenzoate
-
-
peroxynitrite
-
i.e. ONOO-. 0.03-3 mM L-Cys, 0.03-3 mM glutathione, or 0.1-3 mM N-(2-mercaptopropionyl)glycine protects. 1 mM FeSO4 markedly enhances the protection provided by L-Cys, but not by glutathione or N-(2-mercaptopropionyl)glycine
peroxynitrite
-
reacts with [4Fe-4S] cluster yielding an inactive [3Fe-4S] enzyme. Carbon dioxide enhances the reaction. Peroxynitrite also induces aconitase tyrosine nitration, without contributing to inactivation
peroxynitrite
P21399
inactivation due to the release of iron from the Fe-S cluster, other nitric oxide sources decrease the activity of the mitochondrial isozyme
Phthalic acid
-
competitive
pyromellitic acid
-
competitive
Quinaldic acid
-
noncompetitive
Quinaldic acid
Saccharomycopsis lipolytica
-
-
S(1,1,2,2)-tetrafluoroethyl-L-cysteine
Q9ER34
inhibition of renal aconitase activity both in vivo and in vitro is a functional consequence of difluorothioamidyl-L-lysine formation by S(1,1,2,2)-tetrafluoroethyl-L-cysteine
Sodium mersalyl
-
-
succinate
-
-
superoxide anion radical
P28271
-
superoxide anion radical
Q63270
-
threo-Ls-isocitrate
-
competitive
-
trans-aconitate
-
linear competitive
trans-aconitate
-
-
trans-aconitate
P21399
a competitive inhibitor of the enzyme with respect to cis-aconitate and a non-competitive inhibitor with respect to citrate and isocitrate
tricarballylate
-
linear competitive
tricarballylate
-
-
trimellitic acid
-
competitive
trimesic acid
-
competitive
Zn2+
-
inhibition of mitochondrial isoenzyme
Zn2+
-
competitive, the inhibitory effect is specific for the citrate to cis-aconitate reaction; inhibition of mitochondrial isoenzyme; no inhibition of the cytopsolic isoenzyme
Zn2+
-
inhibition of mitochondrial isoenzyme
Zn2+
-
competitive inhibition
Zn2+
P28271
a specific inhibitor of mitochondrial isozyme
Zn2+
Q63270
a specific inhibitor of mitochondrial isozyme
Mn2+
-
inhibition of enzyme, resulting in up to 90% increase in intracellular citrate. Mitochondrial isoform is significantly more sensitive to Mn2+ than cytosolic isoform. Inhibition leads to conversion of enzyme to iron regulatory protein IRP 1 and increases the abundance of IRP2, leading to reduced H-ferritin expression, inreased transferrin receptor expression, and increased uptake of transferrin. IRP2 has a dominant role in Mn2+-induced alteration of iron homeostasis over aconitase/IRP1
additional information
P21399
superoxide inactivates the mRNA-binding activity through direct chemical attack, enzyme competitive inhibition by di- and tricarboxylic acids and inactivation due to modification of cysteine and tyrosine residues, e.g. S-glutathionylation
-
additional information
P28271
superexpression of mitochondrial ferritin in mouse cells leads to iron deficiency in the cytosol, decrease in the level of cytosolic ferritin, and inhibition of cAH and mAH isozyme activities. Enzyme competitive inhibition by di- and tricarboxylic acids, and inactivation due to modification of cysteine and tyrosine residues
-
additional information
Q63270
enzyme competitive inhibition by di- and tricarboxylic acids, and inactivation due to modification of cysteine and tyrosine residues; enzyme competitive inhibition by di- and tricarboxylic acids, and inactivation due to modification of cysteine and tyrosine residues
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
cysteine
-
enzyme activity increases 2-4fold in presence of both Fe2+ and cysteine. 0.1-1 mM Fe2+ and 0.05-0.5 mM cysteine
Fe4-S4 cluster
-
active enzyme contains an iron-sulfur cluster
Fe4-S4 cluster
-
active enzyme contains an iron-sulfur cluster
ferric ammonium citrate
-
increases activity and gene expression
Hemin
-
increases activity and gene expression
lipoic acid
-
causes an increase in cardiac enzyme activity at doses of 35 and 70 mg/kg of 1.3 and 2.4fold in the animals
menadione sodium bisulfite
-
causes a modest activation of IRP-1 to bind to iron resonsive elements within 15-30 min. Menadione-induced oxidative stress leads to post-translational inactivation of both genetic and enzymatic functions of IRP-1 by a mechanism that lies beyond the classical Fe-S cluster switch and exerts multiple effects on cellular iron metabolism
additional information
P28271
the maximal activity requires the presence of sulfhydryl compounds in the medium; the maximal activity requires the presence of sulfhydryl compounds in the medium
-
additional information
Q63270
the maximal activity requires the presence of sulfhydryl compounds in the medium; the maximal activity requires the presence of sulfhydryl compounds in the medium
-
KM VALUE [mM]
KM VALUE [mM] Maximum
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.21
-
(2R,3S)-2-methylisocitrate
P36683
-
0.0035
-
cis-aconitate
-
pH 7.4
0.0048
-
cis-aconitate
-
-
0.007
-
cis-aconitate
-
liver enzyme
0.009
-
cis-aconitate
-
-
0.016
-
cis-aconitate
-
20°C, pH 7.4, enzyme form AcnB
0.018
-
cis-aconitate
Saccharomycopsis lipolytica
-
-
0.0185
-
cis-aconitate
-
pH 8.0, 30°C
0.03
-
cis-aconitate
-
mitochondrial enzyme
0.036
-
cis-aconitate
-
-
0.058
-
cis-aconitate
-
20°C, pH 7.4, enzyme form AcnA
0.099
-
cis-aconitate
-
heart enzyme
0.1
-
cis-aconitate
-
-
0.108
-
cis-aconitate
-
pH 8.4, 75°C
0.12
-
citrate
-
mitochondrial enzyme
0.13
-
citrate
-
-
0.14
-
citrate
-
-
0.2
-
citrate
-
liver enzyme
0.41
-
citrate
-
cytoplasmic isoenzyme
0.48
-
citrate
-
mitochondrial isoenzyme
0.48
-
citrate
-
pH 8.0, 30°C
0.95
-
citrate
-
heart enzyme
1.16
-
citrate
-
20°C, pH 7.4, enzyme form AcnA
1.4
-
citrate
-
isoenzyme II
1.7
-
citrate
-
-
2.9
-
citrate
-
pH 8.4, 75°C
4
4.4
citrate
-
-
10
-
citrate
-
isoenzyme I
11
-
citrate
-
20°C, pH 7.4, enzyme form AcnB
0.012
-
Isocitrate
-
-
0.034
-
Isocitrate
-
liver enzyme
0.045
-
Isocitrate
Saccharomycopsis lipolytica
-
-
0.08
-
Isocitrate
-
cytoplasmic isoenzyme
0.12
-
Isocitrate
-
mitochondrial enzyme
0.139
-
Isocitrate
-
heart enzyme
0.15
-
Isocitrate
-
-
0.32
-
Isocitrate
-
-
0.37
-
Isocitrate
-
pH 8.4, 75°C
0.552
-
Isocitrate
-
pH 8.0, 30°C
0.56
-
Isocitrate
-
pH 8.0, 25°C
0.58
-
Isocitrate
-
-
0.7
-
Isocitrate
-
isoenzyme II
3
-
Isocitrate
Q9NJQ8, Q9NJQ9, -
recombinant enzyme
3.33
-
Isocitrate
-
isoenzyme I
0.0089
-
methyl-cis-aconitate
-
-
-
0.158
-
methyl-cis-aconitate
Saccharomycopsis lipolytica
-
-
-
0.032
-
methylisocitrate
-
-
0.268
-
methylisocitrate
Saccharomycopsis lipolytica
-
-
additional information
-
additional information
-
-
-
additional information
-
additional information
Bos taurus, Saccharomycopsis lipolytica
-
pH-dependence of kinetic parameters
-
additional information
-
additional information
Saccharomycopsis lipolytica
-
-
-
additional information
-
additional information
-
two values are obtained for KM-value with isocitrate as substrate, depending on substrate concentration
-
additional information
-
additional information
-
steady-state kinetics
-
additional information
-
additional information
-
Michaelis-Menten kinetics
-
TURNOVER NUMBER [1/s]
TURNOVER NUMBER MAXIMUM[1/s]
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
3.3
-
cis-aconitate
-
pH 7.4
additional information
-
additional information
-
-
-
additional information
-
additional information
-
-
-
additional information
-
additional information
P36683
-
-
Ki VALUE [mM]
Ki VALUE [mM] Maximum
INHIBITOR
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.81
-
D-glucose 1-phosphate
-
mitochondrial enzyme, with isocitrate as substrate
1.9
-
D-glucose 1-phosphate
-
cytosolic enzyme, with isocitrate as substrate
1.14
-
D-glucose 6-phosphate
-
mitochondrial enzyme, with isocitrate as substrate
2.35
-
D-glucose 6-phosphate
-
cytosolic enzyme, with isocitrate as substrate
0.4
-
fumarate
-
mitochondrial enzyme, with isocitrate as substrate
0.51
-
fumarate
-
cytosolic enzyme, with isocitrate as substrate
0.14
-
glyoxylate
-
mitochondrial enzyme, with isocitrate as substrate
0.42
-
glyoxylate
-
cytosolic enzyme, with isocitrate as substrate
1.81
-
malate
-
cytosolic enzyme, with isocitrate as substrate
2.94
-
malate
-
mitochondrial enzyme, with isocitrate as substrate
0.035
-
nitric oxide
-
reversible inhibition after brief exposure
1.03
-
oxaloacetate
-
mitochondrial enzyme, with isocitrate as substrate
2.8
-
oxaloacetate
-
cytosolic enzyme, with isocitrate as substrate
0.33
-
succinate
-
mitochondrial enzyme, with isocitrate as substrate
0.61
-
succinate
-
cytosolic enzyme, with isocitrate as substrate
1.37
-
trans-aconitate
-
mitochondrial enzyme, with isocitrate as substrate
3.41
-
trans-aconitate
-
cytosolic enzyme, with isocitrate as substrate
IC50 VALUE [mM]
IC50 VALUE [mM] Maximum
INHIBITOR
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
SPECIFIC ACTIVITY [µmol/min/mg]
SPECIFIC ACTIVITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
0.011
0.06
-
aconitate hydratase in blood serum of control rats and rats subjected to myocardial ischemia and treatment with lipoic acid, overview
0.068
0.198
-
aconitate hydratase in myocardium of control rats and rats subjected to myocardial ischemia and treatment with lipoic acid, overview
0.206
-
-
dehydration of citrate to cis-aconitate, pH 8.0, 30°C
0.266
-
-
dehydration of isocitrate to cis-aconitate, pH 8.0, 30°C
0.433
-
-
reverse reaction, hydration of citrate or isocitrate, pH 8.0, 30°C
1.11
-
-
cytoplasmic isoenzyme
1.9
-
P36683
-
2.126
-
Cucurbita sp.
-
isoenzyme Aco II
2.214
-
Cucurbita sp.
-
isoenzyme Aco I
3.4
-
-
mitochondrial isoenzyme
6.13
-
-
mitochondrial enzyme
11.1
-
-
cytosolic enzyme
21.4
-
-
-
118
-
-
pH 8.0, 25°C
additional information
-
-
-
additional information
-
-
-
pH OPTIMUM
pH MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
5.8
-
-
mitochondrial isoenzyme
7.1
-
-
mitochondrial isoenzyme
7.2
7.8
Saccharomycopsis lipolytica
-
-
7.2
-
Rheum sp.
-
phosphate buffer
7.3
-
-
soluble enzyme
7.4
-
Q9ER34
assay at
7.4
-
-
assay at
7.5
8
-
isoenzyme I
7.5
-
-
glycerophosphate buffer
7.5
-
-
isoenzyme II
7.5
-
-
enzyme form AcnA and AcnB, the maximal activity of AcnB is nearly 2fold the activity of AcnA
7.5
-
-
assay at
7.7
-
-
phosphate buffer
7.8
8
-
-
8
8.5
-
-
8
-
-
assay at
8
-
-
assay at
8.1
-
-
N-ethylmorpholine buffer
8.6
-
-
veronal acetate buffer
pH RANGE
pH RANGE MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
5
10
-
pH 5.0: about 75% of maximal activity, pH 10.0: about 60% of maximal activity, AcnA
5.5
9.2
Saccharomycopsis lipolytica
-
about 35% of maximal activity at pH 5.5 and pH 9.2
6
9
-
pH 6: about 55% of maximal activity, pH 9: about 40% of maximal activity, isoenzyme I. pH 6: about 25% of maximal activity, pH 9: about 75% of maximal activity isoenzyme II
6
9
-
pH 6.0: about 55% of maximal activity, pH 9.0: about 20% of maximal activity, AcnB
6.4
8.2
-
pH 6.4: about 60% of maximal activity, pH 8.2: about 75% of maximal activity
TEMPERATURE OPTIMUM
TEMPERATURE OPTIMUM MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
30
35
-
isoenzyme I
30
-
-
isoenzyme II
37
-
-
assay at
TEMPERATURE RANGE
TEMPERATURE MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
20
40
-
about 60% of maximal activity at 20°C and at 40°C, isoenzyme I. 20°C: about 40% of maximal activity, 40°C: about 20% of maximal activity, isoenzyme II
50
90
-
50°C: about 40% of maximal activity, 90°C: about 45% of maximal activity
pI VALUE
pI VALUE MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
5.24
-
P36683
theoretical value
6.5
7.2
-
by IEF-PAGE, identification of 9 different forms with pI-values from 6.5-7.2
7.52
-
-
recombinant isozyme 1, isoelectric focusing
7.65
-
-
recombinant isozyme 2, isoelectric focusing
7.79
-
-
recombinant isozyme 3, isoelectric focusing
8.1
-
-
calculated
SOURCE TISSUE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
SOURCE
-
mesencephalic-derived cell line
Manually annotated by BRENDA team
-
activity is significantly higher in bone marrow of rats treated with N-nitro-L-arginine methylester
Manually annotated by BRENDA team
Q63270
inactive isozyme mAH multimers occur in rat brain in a model of Huntington’s disease
Manually annotated by BRENDA team
-
from fruit juice cells
Manually annotated by BRENDA team
-
two prominent maxima of enzyme activity are measured: the first maximum is found at an early stage of growth, the second lower maximum is detected at the beginning of the expression of the phosphinothricin tripeptide-specific biosynthetic phsA, implying the onset of secondary metabolism
Manually annotated by BRENDA team
Streptomyces viridochromogenes strain Tu494
-
two prominent maxima of enzyme activity are measured: the first maximum is found at an early stage of growth, the second lower maximum is detected at the beginning of the expression of the phosphinothricin tripeptide-specific biosynthetic phsA, implying the onset of secondary metabolism
-
Manually annotated by BRENDA team
Cucurbita sp.
-
etiolated
Manually annotated by BRENDA team
-
repeated contractions increase aconitase activity by 50%. Increase is not accompanied by increase in aconitase protein, but is markedly inhibited by cyclosporin A
Manually annotated by BRENDA team
D3GQL0, D3GQL1, D3GQL2
aconitase isozyme expression profile during fruit development, overview; aconitase isozyme expression profile during fruit development, overview; aconitase isozyme expression profile during fruit development, overview
Manually annotated by BRENDA team
-
gastric carcinoma cell line Okajima
Manually annotated by BRENDA team
-
undifferentiated neonatal cardiomyocyte. In heat-shocked cells aconitase activity is reduced
Manually annotated by BRENDA team
-
changes in enzyme activity in myocardial ischemia are coupled to accumulation of citrate, overview
Manually annotated by BRENDA team
Rattus norvegicus Sprague-Dawley
-
-
-
Manually annotated by BRENDA team
Rheum sp.
-
-
Manually annotated by BRENDA team
-
epithelium
Manually annotated by BRENDA team
-
activity is significantly higher in liver of rats treated with N-nitro-L-arginine methylester
Manually annotated by BRENDA team
-
under normal conditions and during toxic hepatitis. Toxic hepatitis is accompanied by inactivation of aconitate hydratase
Manually annotated by BRENDA team
P21399, Q99798
purified human CD34+ progenitors derived from granulocyte-colony stimulating factor mobilized peripheral blood cells of normal donors; purified human CD34+ progenitors derived from granulocyte-colony stimulating factor mobilized peripheral blood cells of normal donors
Manually annotated by BRENDA team
-
malignant and nonmalignant tissues
Manually annotated by BRENDA team
P21399
mitochondrial isozyme plays the key role in the bioenergetic theory of malignant transformation of the prostate; mitochondrial isozyme plays the key role in the bioenergetic theory of malignant transformation of the prostate
Manually annotated by BRENDA team
-
muscle exercise does not affect aconitase activity despite increased oxidative stress
Manually annotated by BRENDA team
-
repeated contractionsdo not alter aconitase activity
Manually annotated by BRENDA team
-
activity is significantly higher in spleen of rats treated with N-nitro-L-arginine methylester
Manually annotated by BRENDA team
-
pulvinus bundle sheath cells
Manually annotated by BRENDA team
Q9ER34
mitochondrial aconitase is over-expressed in primary mesencephalic cultures
Manually annotated by BRENDA team
additional information
-
the carbon source, e.g. glucose, sucrose, glycerol, or sunflower oil, influences the citrate/isocitrate ratio in the cells, overview
Manually annotated by BRENDA team
additional information
P21399
isozymes cAH and mAH are present in all tissues, and are most active in the heart, kidney, and liver
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
-
identical with iron-responsive element binding protein
Manually annotated by BRENDA team
-
79% cytosolic enzyme and 21% mitochondrial enzyme for control animals, 83% cytosolic enzyme and 17% mitochondrial enzyme for starving animals
Manually annotated by BRENDA team
-
3 cytosolic aconitases: C1, C2 and C3
Manually annotated by BRENDA team
-
isoforms Aco1, Aco2, Aco3. Cytosolic aconitase is not converted into an iron-responsive element and does not regulate iron homeostasis
Manually annotated by BRENDA team
-
cytosolic isoform
Manually annotated by BRENDA team
P21399
cytosolic isozyme cAH, IRP1 is a cytosolic isozyme devoid of labile Fe2+
Manually annotated by BRENDA team
P28271
cytosolic isozyme cAH; IRP1 is a cytosolic isozyme devoid of labile Fe2+
Manually annotated by BRENDA team
Q63270
cytosolic isozyme cAH; IRP1 is a cytosolic isozyme devoid of labile Fe2+
Manually annotated by BRENDA team
-
cytoplasmic aconitase
Manually annotated by BRENDA team
-
aconitase in yeast is a single translation product, which is dual targeted and distributed between the mitochondria and the cytosol by a unique mechanism involving reverse translocation, dual localization, detailed overview
Manually annotated by BRENDA team
-
soluble isozyme
Manually annotated by BRENDA team
-
aconitase in yeast is a single translation product, which is dual targeted and distributed between the mitochondria and the cytosol by a unique mechanism involving reverse translocation, dual localization, detailed overview
-
Manually annotated by BRENDA team
Cucurbita sp.
-
very low activity
Manually annotated by BRENDA team
-
particulate-bound mitochondrial enzyme, the soluble mitochondrial enzyme is released from the mitochondria by freezing and thawing
Manually annotated by BRENDA team
-
79% cytosolic enzyme and 21% mitochondrial enzyme for control animals, 83% cytosolic enzyme and 17% mitochondrial enzyme for starving animals
Manually annotated by BRENDA team
-
2 mitochondrial aconitases: M1 and M2
Manually annotated by BRENDA team
-
24 h after intraperitoneal administration of endotoxin, there is a 28% reduction in mitochondrial respiration and a 24% reduction in aconitase activity. Functional activity of the electron transport chain is unaffected
Manually annotated by BRENDA team
-
acclimation at 28°C results in strong decrease in enzyme mRNA and activity as well as in LON protease mRNA and activity
Manually annotated by BRENDA team
-
mitochondrial isoform
Manually annotated by BRENDA team
-
analysis of mitochondrial proteome, identification of two particular N-formylkynurenine modifications of enzyme
Manually annotated by BRENDA team
-
significant decrease in activity with age, accompanied by relatively subtle alterations in activities of other citric acid cycle enzymes. Changes contribute to a decline in overall efficiency of mitochondrial bioenegetics with age
Manually annotated by BRENDA team
-
enzyme is a component of mitochondrial DNA nucleoids
Manually annotated by BRENDA team
P21399
mitochondrial isozyme mAH
Manually annotated by BRENDA team
P28271
mitochondrial isozyme mAH
Manually annotated by BRENDA team
Q63270
mitochondrial isozyme mAH
Manually annotated by BRENDA team
-
mitochondrial aconitase activity represents up to 80% of the total aconitase activity in skin fibroblasts
Manually annotated by BRENDA team
-
aconitase in yeast is a single translation product, which is dual targeted and distributed between the mitochondria and the cytosol by a unique mechanism involving reverse translocation, dual localization, detailed overview
Manually annotated by BRENDA team
-
mitochondrial isozyme
Manually annotated by BRENDA team
Rattus norvegicus Sprague-Dawley
-
-
-
Manually annotated by BRENDA team
-
aconitase in yeast is a single translation product, which is dual targeted and distributed between the mitochondria and the cytosol by a unique mechanism involving reverse translocation, dual localization, detailed overview
-
Manually annotated by BRENDA team
Saccharomyces cerevisiae MMY011
-
-
-
Manually annotated by BRENDA team
additional information
-
subcellular localization study, overview. All mutant aconitase protein molecules are partially imported into mitochondria, then the N-terminal mitochondrial targeting sequence is cleaved off by the mitochondrial processing peptidase. After the cleavage, a subpopulation of the protein molecules moves back into the cytosol by reverse translocation. The aconitase C-terminal domain confers dual targeting
-
Manually annotated by BRENDA team
additional information
-
subcellular localization study, overview. All mutant aconitase protein molecules are partially imported into mitochondria, then the N-terminal mitochondrial targeting sequence is cleaved off by the mitochondrial processing peptidase. After the cleavage, a subpopulation of the protein molecules moves back into the cytosol by reverse translocation. The aconitase C-terminal domain confers dual targeting
-
-
Manually annotated by BRENDA team
MOLECULAR WEIGHT
MOLECULAR WEIGHT MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
66000
-
-
gel filtration
67000
-
-
gel filtration
68500
-
-
equilibrium sedimentation
75000
80000
-
isoenzyme II, gel filtration
79000
-
-
ultracentrifugation
80900
-
-
low speed equilibrium sedimentation
84000
-
-
mitochondrial enzyme, gel filtration
89000
-
-
equilibrium sedimentation
95000
-
-
gel filtration
96000
-
-
cytosolic enzyme, gel filtration
100000
-
Cucurbita sp.
-
isoenzyme Aco I and Aco II, gel filtration
100000
-
-
gel filtration
114000
-
-
recombinant N-terminally His-tagged aconitase, gel filtration
122000
-
-
recombinant aconitase with an additional Gly at the C-terminus, gel filtration
145000
-
-
gel filtration
150000
160000
-
isoenzyme I, gel filtration
150000
-
-
gel filtration
additional information
-
-
partial amino acid sequence
SUBUNITS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
?
-
x * 82754, calculation from nucleotide sequence
?
P36683
x * 94000, SDS-PAGE
?
-
x * 96000, SDS-PAGE
?
-
x * 96000, SDS-PAGE
?
Q9NFX2, Q9NFX3
x * 100000, SDS-PAGE; x * 100000, SDS-PAGE
?
-
x * 87606, calculated. By IEF-PAGE, identification of 9 different forms of 91000-93000 Da
?
Q63270
x * 95000-100000, IRP1, SDS-PAGE
?
-
x * 80000, recombinant enzyme, SDS-PAGE, x * 85700, sequence calculation
?
Escherichia coli W3350
-
x * 94000, SDS-PAGE
-
?
Paracoccidioides brasiliensis ATCC MYA 826
-
x * 80000, recombinant enzyme, SDS-PAGE, x * 85700, sequence calculation
-
dimer
-
2 * 41000, mitochondrial enzyme, SDS-PAGE; 2 * 45000, cytosolic enzyme, SDS-PAGE
homodimer
P25516, P36683
structural modeling, homo-oligomerization of AcnA yields negative cooperativities in isomerization of isocitrate. In the AcnA homodimer, the intersubunit interface is composed of domains II and III. The iron-sulfur cluster, which constitutes the active site, is located at the interdomain boundary among the three domains, overview; structural modeling, homo-oligomerization of AcnB yields negative cooperativities in isomerization of isocitrate. In the AcnA homodimer, the intersubunit interface is composed of domains II and III. The iron-sulfur cluster, which constitutes the active site, is located at the interdomain boundary among the three domains, overview
homodimer
-
structural analysis by X-ray scattering and modelling of wild-type and mutant enzymes, overview
monomer
-
1 * 120000, SDS-PAGE
monomer
-
1 * 83000, SDS-PAGE
monomer
Cucurbita sp.
-
1 * 89000, isoenzyme Aco I and Aco II, SDS-PAGE
monomer
-
1 * 97500, SDS-PAGE
monomer
-
1 * 102000, SDS-PAGE
monomer
-
1 * 104800, recombinant N-terminally His-tagged aconitase, sequence calculation, 1 * 102300, recombinant aconitase with an additional Gly at the C-terminus, sequence calculation
monomer
-
1 * 104800, recombinant N-terminally His-tagged aconitase, sequence calculation, 1 * 102300, recombinant aconitase with an additional Gly at the C-terminus, sequence calculation
-
additional information
-
the [4Fe-4S] cluster loaded form of the IscU [Fe-s] cluser scaffolding protein can be used for intact cluster transfer to an apo form of aconitase A. IscU mutant D39A is an effective inhibitor of IscU-directed activation of apo-aconitase A
additional information
-
enzyme binds to the 3’ untranslated region of transcriptional activator GerE mRNA in in vitro gel shift assays
additional information
P21399
depending on the conditions, the enzyme can associate to dimer, trimer, and tetramer forms, followed by the loss of enzyme activity; depending on the conditions, the enzyme can associate to dimer, trimer, and tetramer forms, followed by the loss of enzyme activity
additional information
Q9ER34
peptide mapping, mass spectrometry analysis, overview
additional information
D3GQL0, D3GQL1, D3GQL2
Aco1 domain structure, comparison to Aco3 and Aco2 and to enzymes from Arabidopsis thaliana, overview; Aco2 domain structure, comparison to Aco1 and Aco3 and to enzymes from Arabidopsis thaliana, overview; Aco3 domain structure, comparison to Aco1 and Aco2 and to enzymes from Arabidopsis thaliana, overview
additional information
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peptide mapping and proteomic analysis, overview
additional information
Paracoccidioides brasiliensis ATCC MYA 826
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peptide mapping and proteomic analysis, overview
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POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
phosphoprotein
-
S711 is a phosphorylation site
phosphoprotein
-
S711 of IRP1 is phosphorylated by proteinkinase C in vitro and in vivo in human HEK cells. Aconitase activity of the S711 phosphomimetic mutants is preferentially inhibited in the citrate mode of aconitase function. The substitution of phosphomimetic amino acids for S711 fails to affect the RNA-binding affinity of IRP1
phosphoprotein
P21399
mechanism controlling IRP1 activity at the level of its stability can be phosphorylation of Ser138, Ser138, Ser711, and flanking sequences are highly conserved
phosphoprotein
-
aconitase is phosphorylated on serine residues. Increase in extensor digitorum longus muscle enzyme activity upon repeated contraction is inhibited by cyclosporin A, an inhibitor of the protein phosphates calcineurin
phosphoprotein
Q9ER34
phosphorylation of mitochondrial aconitase by PKCbeta2 has regulatory function, overview
side-chain modification
-
traces of carbohydrate of less than 1%
proteolytic modification
-
the porcine heart enzyme is synthesized as a precursor containing a mitochondrial targeting sequence of 27 amino acid residues which is cleaved to yield a mature enzyme of 754 amino acids
side-chain modification
-
traces of carbohydrate of less than 1%
additional information
-
identification of two mitochondrial forms of enzyme with N-formylkynurenine modifications
side-chain modification
-
traces of carbohydrate of less than 1%
additional information
-
a postranslational activation-inactivation mechanism might be operating
Crystallization/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
crystal structure of enzyme-fluorocitrate complex
-
2.4 A structure of AcnB, hanging drop vapor diffusion at 17°C
-
aconitase form of bifunctional enzyme, evaluation of model for iron regulatory form of enzyme and its binding to iron-responsive elements
P21399
recombinant enzyme, hanging-drop vapour-diffusion method. An X-ray fluorescence measurement performed on a gold-derivative crystal shows the unexpected presence of zinc, in addition to gold and iron
-
1.8 A resolution crystal structure of the S642A:citrate complex of mitochondrial aconitase
P16276
computational modeling of aconitase inactivation by superoxide and nitric oxide
-
crystallographic evidence for a three-iron center
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TEMPERATURE STABILITY
TEMPERATURE STABILITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
5
-
-
15 h, 50% inactivation, isoenzyme I. 15 h, about 65% loss of activity, isoenzyme II
30
-
-
5 h, 50% loss of activity, isoenzyme II. 15 h, 90% loss of activity, isoenzyme I. 15 h, 75% loss of activity, isoenzyme II
45
-
-
complete inactivation after 20 min without fluorocitrate, stable in presence of fluorocitrate 0.05 mM, 40% loss of activity in presence of 20 mM citrate
50
-
-
30 min, stable
60
-
-
10 min, complete inactivation
80
-
-
1 h, stable under strictly anaerobic conditions
80
-
-
1 h, stable
95
-
-
half-life: 14 min
GENERAL STABILITY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
freezing and thawing inactivates aconitase in absence of glycerol or sucrose
Cucurbita sp.
-
fluorocitrate protects from inactivation by O2
-
more than 50% of total aconitase activity is lost when cell-free extracts are prepared under air by a French press, by osmotic rupture of spheroplasts or by sonic treatment
-
fluorocitrate stabilizes against heat inactivation
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OXIDATION STABILITY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
fluorocitrate protects from inactivation by O2
-
33804
rapid inactivation by exposure to air
P36683
488175
high oxygen sensitivity
-
651095
STORAGE STABILITY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
-20°C, 25% w/v glycerol, stable for several weeks
Cucurbita sp.
-
4°C, activity of the highly purified cytosolic enzyme decreases by 15-20% during the first 24 h of storage and then by 5% every 24 h, the mitochondrial enzyme decreases 35-40% during the first 24 h and then by 15% every 24 h
-
-20°C, enzyme frozen after dialysis against 0.05 M Tris-HCl, pH 7.5, complete inactivation after 10 days
-
4°C, 24 h, pH 5.5-9.0, stable
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Purification/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
recombinant His-tagged aconitase from Escherichia coli strain BL21(DE3) by nickel affinty chromatography and gel filtration, removal of the His tag by factor Xa and further purification, or purification of recombinant aconitase, expressed from plasmid pTYB2-acn in Escherichia coli, using chitin beads, overview
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isoenzymes Aco I and Aco II
Cucurbita sp.
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recombinant protein; recombinant protein
Q9NFX2, Q9NFX3
AcnA and AcnB
-
enzyme form AcnA
-
native and SeMet [3Fe-4S] form of AcnB expressed in Escherichia coli
-
recombinant AcnB5-4 polypeptide
-
recombinant enzymes from Escherichia coli strain BL21(DE3) by gel filtration
-
recombinant His-tagged AcnA by metal affinity chromatography; recombinant His-tagged AcnB by metal affinity chromatography
P25516, P36683
recombinant IRP1
-
native IRP1 from liver
Q63270
partially, isolation of mitochondria
-
using column chromatography
-
-
Saccharomycopsis lipolytica
-
using Ni-NTA chromatography
-
-
Q9NJQ8, Q9NJQ9, -
Cloned/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
expression of wild-type and mutant enzymes in Escherichia coli strain DH5alpha, and in Bacillus subtilis strains GWH1025 and GWH1026, respectively
-
expression in HEK 293 cells
Q23500
gene Ccaco1, DNA and amino acid sequence determination, sequence comparisons and phylogenetic analysis; gene Ccaco2, DNA and amino acid sequence determination, sequence comparisons and phylogenetic analysis; gene Ccaco2, DNA and amino acid sequence determination, sequence comparisons and phylogenetic analysis
D3GQL0, D3GQL1, D3GQL2
expression of N-terminally His-tagged aconitase in Escherichia coli strain BL21(DE3), alternative expression method uses overexpression of aconitase from plasmid pTYB2-acn, resulting in an aconitase containing only an additional glycine residue at the C-terminus
-
overexpression in Escherichia coli, His-tag; overexpression in Escherichia coli, His-tag
Q9NFX2, Q9NFX3
AcnB domain 5-4 polypeptide is expressed in Escherichia coli as a GST-AcnB5-4 fusion protein
-
gene AcnA, overexpression of the His-tagged protein in an ASKA library, i.e. the 'a complete set of Escherichia coli K-12 ORF archive library; gene ACnB, overexpression of the His-tagged protein in an ASKA library
P25516, P36683
gene acnB, expression of wild-type enzyme and the fusion protein ICDH-AcnB in Escherichia coli strain BL21 (DE3)
-
gene Pbaco, quantitative real-time RT-PCR expression analysis, recombinant expression in Saccharomyces cerevisiae, ACO is present in the extracellular fluid, cell wall enriched fraction, mitochondria, cytosol and peroxisomes of yeast cells
-
gene Aco2
Q9ER34
expression in Bacillus subtilis
-
expression in Escherichia coli
-
expression of wild-type enzyme and diverse pount and deletion mutants
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the recombinant yeast mitochondrial aconitase is expressed in Escherichia coli as soluble, biologically active enzyme
-
yeast mitochondrial aconitase is expressed in Escherichia coli by cultivation in a bioreactor at different temperatures. Chaperones GroEL and GroES are co-expressed
-
expressed in Escherichia coli as a His-tagged fusion protein
-
expression in Escherichia coli
-
expression in Escherichia coli
-
expression in Escherichia coli
Q9NJQ8, Q9NJQ9, -
gene ACO1, overexpression in strain H222, high-level expression of ACO in the ACO1 multicopy integrative transformant results in a shift of the citric acid/isocitric acid product pattern into the direction of isocitric acid
-
cytoplasmic aconitase/iron regulatory protein 1 expression analysis, overview
-
EXPRESSION
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
citramalate significantly increases citrate content and reduces the mitochondrial isozyme activity, while slightly inducing its protein level, oxalomalate also slightly upregulates the enzyme
-
acetate and ethanol as sole carbon sources and in high iron conditions induce the enzyme
-
acetate and ethanol as sole carbon sources and in high iron conditions induce the enzyme
Paracoccidioides brasiliensis ATCC MYA 826
-
-
ENGINEERING
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
C517A
-
enzymatically inactive mutant enzyme that still binds iron responsive elements
R740E/Q744E/F661L/I809T/V852A
-
sixfold increase in specific activity compared to wild-type. Mutant strain is defective in sporulation, affecting the expression of deltaK-dependent genes. Accumulation of transcriptional activator GerE mRNa and protein is delayed in the mutant
R741E/Q745E
-
site-directed mutagenesis, the mutant strain exhibits an increased enzymatic activity of aconitase comparing to that of the wild-type strain, because the aconitase protein expression level is significantly increased in the mutant strain
S711A
-
citrate-to-isocitrate aconitase activity is about 70% of the wild-type activity, isocitrate-to-cis-aconitate activity is about 90% of wild-type activity
S711D
-
no citrate-to-isocitrate aconitase activity, isocitrate-to-cis-aconitate activity is identical to wild-type activity
S711E
-
45% of the capacity to catalyze conversion of cis-aconitase into isocitrate, completely fails to bind RNA and to generate isocitrate from citrate
S711E
-
citrate-to-isocitrate aconitase activity is about 10% of the wild-type activity, isocitrate-to-cis-aconitate activity is about 20% of wild-type activity
C381A
-
site-directed mutagenesis
C447A
-
site-directed mutagenesis
C381A
-
site-directed mutagenesis
-
C447A
-
site-directed mutagenesis
-
additional information
-, B3TZE0
transposon mutagenesis. In one disulfide 3,3’-dithiodipropionic acid (DTDP)-negative (Jhw13b) and one DTDP-leaky (JhwAA14) mutant, Tn5::mob is mapped in a gene encoding a putative bifunctional aconitate hydratase 2/2-methylisocitrate dehydratase (AcnB, EC 4.2.1.3). AcnB dehydrates 2-methylcitric acid to 2-methyl-cis-aconitic acid and subsequently hydrates it to 2-methylisocitric acid
additional information
Advenella kashmirensis DPN7T
-
transposon mutagenesis. In one disulfide 3,3’-dithiodipropionic acid (DTDP)-negative (Jhw13b) and one DTDP-leaky (JhwAA14) mutant, Tn5::mob is mapped in a gene encoding a putative bifunctional aconitate hydratase 2/2-methylisocitrate dehydratase (AcnB, EC 4.2.1.3). AcnB dehydrates 2-methylcitric acid to 2-methyl-cis-aconitic acid and subsequently hydrates it to 2-methylisocitric acid
-
additional information
-
loss-of-fucntion mutants of isoforms Aco1, Aco2, Aco3. Plants with mutations aco1 or aco3 show a clear decrease in cytosolic aconitase activity. None of the mutants is affected in respect of the accumulation of the ferritin transcript or protein response to iron excess
additional information
-
enzyme knock-out plants have significantly less chlorosis after treatment with the superoxide-generating compound paraquat, show delayed induction of the antioxidant gene GST1 and inceased levels of chloroplastic CuZn superoxide dismutase 2 mRNA
R741E/Q745E
Bacillus subtilis NK1010
-
site-directed mutagenesis, the mutant strain exhibits an increased enzymatic activity of aconitase comparing to that of the wild-type strain, because the aconitase protein expression level is significantly increased in the mutant strain
-
additional information
Q9NFX2, Q9NFX3
isoform IRP-1A specific overexpression in muscle results in pre-adult lethality
additional information
-
construction of a fusion protein of aconitase B and isocitrate dehydrogenase, ICDH and AcnB, i.e. ICDH-AcnB, structure determination of ICDH-AcnB, overview
additional information
P21399
naturally occuring IRP1 has no [Fe-S] cluster and is devoid of aconitase activity due to the absence of cysteine residues binding the [Fe-S] cluster in the active center
S711T
-
citrate-to-isocitrate aconitase activity is about 60% of the wild-type activity, isocitrate-to-cis-aconitate activity is about 60% of wild-type activity
additional information
P28271
naturally occuring IRP1 has no [Fe-S] cluster and is devoid of aconitase activity due to the absence of cysteine residues binding the [Fe-S] cluster in the active center
additional information
-
virus-induced gene silencing of enzyme causes a 90% reduction in its activity, leading to stunting, spontaneous necrotic lesions, and increased resistance to paraquat. Silenced plants show less cell death after transient co-expression of the AvrPto and Pto proteins or the pro-apoptotoc protein Bax. Silenced plants expressing the Pto transgene display a delayed hypersensitive response and support higher levels of bacterial growth
additional information
Q63270
naturally occuring IRP1 has no [Fe-S] cluster and is devoid of aconitase activity due to the absence of cysteine residues binding the [Fe-S] cluster in the active center
H170A
-
site-directed mutagenesis
additional information
-
overexpression of enzyme in Escherichia coli. Presence of co-expressed GroEL reduces the aconitase over-expression drastically, however, exogenous GroEL and GroES together compensate this reduction. For over-expressing cells, growth-rate decreases by 30% at 25°C, however, in presence of co-expressed GroEL and GroES the growth rate of aconitase producing cells is enhanced by 30% at 37°C
additional information
-
transgenic expression of yeast enzyme in Bacillus subtilis aconitase null mutant restores aconitase activity and glutamate prototrophy, but only partially restores sporulation. Late sporulation gene expression in the transgenic strain is delayed
additional information
-
the gene aco1 deficient mutant aco1DELTA shares several growth phenotypes as well as patterns of specific protein expression with a Saccharomyces cerevisiae mutants lacking mitochondrial NAD+-specific isocitrate dehydrogenase idhDELTA, these phenotypes are eliminated by co-disruption of the CIT1 gene encoding mitochondrial citrate synthase, effects of citrate, iron, and pH, overview
additional information
-
construction of diverse deletion mutants of aconitase, overview. Deletion of six C-terminal amino acids does not eliminate enzymatic activity but abolishes dual targeting
H170A
-
site-directed mutagenesis
-
additional information
-
construction of diverse deletion mutants of aconitase, overview. Deletion of six C-terminal amino acids does not eliminate enzymatic activity but abolishes dual targeting
-
additional information
Saccharomyces cerevisiae MMY011
-
the gene aco1 deficient mutant aco1DELTA shares several growth phenotypes as well as patterns of specific protein expression with a Saccharomyces cerevisiae mutants lacking mitochondrial NAD+-specific isocitrate dehydrogenase idhDELTA, these phenotypes are eliminated by co-disruption of the CIT1 gene encoding mitochondrial citrate synthase, effects of citrate, iron, and pH, overview
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APPLICATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
environmental protection
-
use of enzyme as biomarker of oxidative damage. Exposure of oysters to Cd2+ results in elevated production of reactive oxygen species and enzyme inhibition, which is particualrly pronounced at elevated temperature
medicine
-
mitochondrial enzyme is present in the glandular epithelium of normal glands, hyperplastic glands, adenocarcinomatous glands, and prostatic intraepithelial neoplastic fold. There is no difference in enzyme levels between malignant and non-malignant tissues
medicine
-
enzyme inhibition, e.g. by deferiprone, is helpful in Friedreich's ataxia treatment
medicine
-
it is shown that the cytosolic aconitase defect and consequent IRP1 activation occurring in Friedreich's Ataxia (FRDA) cells are reversed by the action of extramitochondrial frataxin
biotechnology
-
molecular chaperones GroEL/GroES are co-expressed with soluble, biologically active recombinant aconitase in Escherichia coli by cultivation in a bioreactor at different temperatures under optimized conditions. The yield of functional aconitase is enhanced, either in presence of co-expressed GroEL/ES or at low temperature cultivation. The outcome from the chaperone assisted folding of aconitase is more pronounced at lower temperature
synthesis
-
overexpression of enzyme in Escherichia coli. Presence of co-expressed GroEL reduces the aconitase over-expression drastically, however, exogenous GroEL and GroES together compensate this reduction. For over-expressing cells, growth-rate decreases by 30% at 25°C, however, in presence of co-expressed GroEL and GroES the growth rate of aconitase producing cells is enhanced by 30% at 37°C