ACO2 (Aconitase 2)

Aconitase employs a cluster to catalyze the stereospecific dehydration-rehydration of citrate to isocitrate via cis-aconitase in the second and third steps of the Krebs cycle. The protein contains four domains; the first three from the N-terminus are closely associated around the [3Fe-4S] cluster with all three cysteine ligands to the cluster being provided by the third domain. Association of the larger C-terminal domain with the first three domains creates an extensive cleft leading to the Fe-S cluster. Residues from all four domains contribute to the active site region, which is defined by the Fe-S cluster. This region of the structure contains 4 Arg, 3 His, 3 Ser, 2 Asp, 1 Glu, 3 Asn, and 1 Gln residues, as well as several bound water molecules. Three of these side chains reside on a three turn 310 helix in the first domain. Diseases relevant to aconitase are aconitase deficiency, Friedreich's ataxia (FRDA), and diabetes. Aconitase deficiency is caused by mutation in the gene for iron-sulfur cluster scaffold protein, which helps to form the Fe-S cluster. FRDA is caused when the Fe-S proteins in aconitase and succinate dehydrogenase have decreased activity. ACO2 is the mitochondrial form of aconitase different from the soluble form ACO1.

ACO2 (Aconitase 2) Related Areas

Enzyme >>Carbohydrate Metabolism Enzymes >>ACO2

ACO2 (Aconitase 2) Alternative Names

ACONM, MGC20605, MGC33908 [Homo sapiens]

Aco-2, Aco3, D10Wsu183e[Mus musculus]

Summaries for ACO2 (Aconitase 2)

Entrez Gene summary for ACO2:

The protein encoded by this ACO2 gene belongs to the aconitase/IPM isomerase family. ACO2 is an enzyme that catalyzes the interconversion of citrate to isocitrate via cis-aconitate in the second step of the TCA cycle. ACO2 is encoded in the nucleus and functions in the mitochondrion. ACO2 was found to be one of the mitochondrial matrix proteins that are preferentially degraded by the serine protease 15(PRSS15), also known as Lon protease, after oxidative modification. [provided by RefSeq, Jul 2008]

Human ACO2 (Aconitase 2) Protein General Information

 

• Protein names: Aconitate hydratase, mitochondrial, Short name=Aconitase
• Sequence length: 780 AA.
• Catalytic activity: Citrate = isocitrate.
• Sequence similarities: ACO2 belongs to the aconitase/IPM isomerase family.
• Cofactor: ACO2 binds 1 4Fe-4S cluster per subunit. Binding of a 3Fe-4S cluster leads to an inactive enzyme
• Subunit structure: Monomer
• Subcellular location: Mitochondrion
• Pathway: Carbohydrate metabolism; tricarboxylic acid cycle; isocitrate from oxaloacetate: step 2/2.
• Involvement in disease: Defects in ACO2 are the cause of infantile cerebellar-retinal degeneration (ICRD) [MIM:614559]. A severe autosomal recessive neurodegenerative disorder characterized by onset between ages 2 and 6 months of truncal hypotonia, athetosis, seizures, and ophthalmologic abnormalities, particularly optic atrophy and retinal degeneration. Affected individuals show profound psychomotor retardation, with only some achieving rolling, sitting, or recognition of family. Brain MRI shows progressive cerebral and cerebellar degeneration.

General information above from UniProt

Function for ACO2 (Aconitase 2) Protein

UniProtKB:

ACO2 catalyzes the isomerization of citrate to isocitrate via cis-aconitate.

Genatlas:

• ACO2 is involved in the second step of citric acid cycle
• ACO2 plays an important role in the unique pathway of citrate accumulation in prostate epithelial cells through its limited activity
• ACO2 is key enzyme in citrate oxidation in prostate epithelial cells, and its abnormal expression has been implicated in tumorigenesis of the prostate

Homology for human ACO2 (Aconitase 2)

• ortholog to murine Aco2
• ortholog to rattus aco2

Phenotype Information for ACO2 (Aconitase 2)

• Gene/Locus: ACO2, ICRD
• Phenotype: Infantile cerebellar-retinal degeneration

Phenotype Information for ACO2 from OMIM (Online Mendelian Inheritance in Man)