Aconitase

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Illustration of  pig aconitase in complex with the [Fe4S4] cluster, PDB ID 7ACN. The protein is colored by secondary structure, and iron atoms are blue and the sulfur red.
Illustration of pig aconitase in complex with the [Fe4S4] cluster, PDB ID 7ACN. The protein is colored by secondary structure, and iron atoms are blue and the sulfur red.
aconitase 1, soluble
Identifiers
Symbol ACO1
Alt. Symbols IREB1
Entrez 48
HUGO 117
OMIM 100880
RefSeq NM_002197
UniProt P21399
Other data
EC number 4.2.1.3
Locus Chr. 9 p21.1
aconitase 2, mitochondrial
Identifiers
Symbol ACO2
Entrez 50
HUGO 118
OMIM 100850
RefSeq NM_001098
UniProt Q99798
Other data
EC number 4.2.1.3
Locus Chr. 22 q13.2

Aconitase (aconitate hydratase; EC 4.2.1.3) is an enzyme that catalyses the stereo-specific isomerization of citrate to isocitrate via cis-aconitate in the tricarboxylic acid cycle, a non-redox-active process.

[edit] Function

By contrast with the majority of iron-sulfur proteins that function as electron carriers, the iron-sulfur cluster of aconitase reacts directly with an enzyme substrate. Aconitase has an active [Fe4S4]2+ cluster, which may convert to an inactive [Fe3S4]+ form. Three cysteine (Cys) residues have been shown to be ligands of the [Fe4S4] centre. In the active state, the labile iron ion of the [Fe4S4] cluster is not coordinated by Cys but by water molecules.

The iron-responsive element binding protein (IRE-BP) and 3-isopropylmalate dehydratase (α-isopropylmalate isomerase; EC 4.2.1.33), an enzyme catalysing the second step in the biosynthesis of leucine, are known aconitase homologues. Iron regulatory elements (IREs) constitute a family of 28-nucleotide, non-coding, stem-loop structures that regulate iron storage, heme synthesis and iron uptake. They also participate in ribosome binding and control the mRNA turnover (degradation). The specific regulator protein, the IRE-BP, binds to IREs in both 5' and 3' regions, but only to RNA in the apo form, without the Fe-S cluster. Expression of IRE-BP in cultured cells has revealed that the protein functions either as an active aconitase, when cells are iron-replete, or as an active RNA-binding protein, when cells are iron-depleted. Mutant IRE-BPs, in which any or all of the three Cys residues involved in Fe-S formation are replaced by serine, have no aconitase activity, but retain RNA-binding properties.

Aconitase is inhibited by fluoroacetate, therefore fluoroacetate is poisonous.

[edit] References

  • Beinert, H., Kennedy, M.C. and Stout, C.D. (1996). "Aconitase as iron-sulfur protein, enzyme, and iron-regulatory protein". Chem. Rev. 96: 2335–2373. doi:10.1021/cr950040z. 
  • Flint, D.H. and Allen, R.M. (1996). "Iron-sulfur proteins with nonredox functions". Chem. Rev. 96: 2315–2334. doi:10.1021/cr950041r. 
  • Frishman, D. and Hentze, M.W. (1996). "Conservation of aconitase residues revealed by multiple sequence analysis". Eur. J. Biochem. 239: 197–200. doi:10.1111/j.1432-1033.1996.0197u.x. 

[edit] External links

  • 7ACN - PDB structure of pig aconitase in complex with [Fe4S4] cluster and isocitrate
  • 1L5J - PDB structure of Escherichia coli aconitase complexed with [Fe3S4] cluster and aconitate
  • IPR000573 - InterPro entry for aconitase
  • MeSH Aconitase