(aconitate hydratase; EC 188.8.131.52
) is an enzyme that catalyses the stereo-specific isomerization
in the tricarboxylic acid cycle
, a non-redox
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 [Fe4
cluster, which may convert to an inactive [Fe3
form. Three cysteine
(Cys) residues have been shown to be ligands of the [Fe4
] centre. In the active state, the labile iron
ion of the [Fe4
] 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 184.108.40.206), 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.
- 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.
- Flint, D.H. and Allen, R.M. (1996). "Iron-sulfur proteins with nonredox functions". Chem. Rev. 96 2315–2334.
- Frishman, D. and Hentze, M.W. (1996). "Conservation of aconitase residues revealed by multiple sequence analysis". Eur. J. Biochem. 239 197–200.
- 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