Aconitase (aconitate hydratase; EC 4.2.1.3) catalyses the stereo-specific isomerization of citrate to isocitrate via cis-aconitate in the tricarboxylic acid cycle, a non-redox-active process. EC numbers (Enzyme Commission numbers) are a numerical classification scheme for enzymes, based on the chemical reactions they catalyze. ... The citrate ion can be written C3H5O(COO)33-, that is, citric acid minus three hydrogen ions. ... The citric acid cycle (also known as the tricarboxylic acid cycle, the TCA cycle, or the Krebs cycle) is a series of chemical reactions of central importance in all living cells that utilize oxygen as part of cellular respiration. ...

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. Iron-sulfur proteins are proteins characterized by the presence of polymetallic systems (iron-sulfur clusters) containing sulfide ions, in which the iron ions have variable oxidation states. ... An iron-sulfur cluster is a structural motif found in certain metalloproteins, such as the ferredoxins, as well as NADH dehydrogenase and Coenzyme Q - cytochrome c reductase of the electron transfer system. ... Cysteine is a naturally occurring hydrophobic amino acid which has a sulfhydryl group and is found in most proteins, however only in small quantities. ... General Name, Symbol, Number iron, Fe, 26 Chemical series transition metals Group, Period, Block 8, 4, d Appearance lustrous metallic with a grayish tinge Atomic mass 55. ...

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. EC numbers (Enzyme Commission numbers) are a numerical classification scheme for enzymes, based on the chemical reactions they catalyze. ... Leucine is one of the 20 most common amino acids and coded for by DNA. It is isomeric with isoleucine. ... A hæm or heme is a metal-containing cofactor that consists of an iron atom contained in the center of a large heterocyclic organic ring called a porphyrin. ... Figure 1: Ribosome structure indicating small subunit (A) and large subunit (B). ... The interaction of mRNA in a eukaryote cell. ... Serine is one of the 20 most common natural amino acids on Earth. ...

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.
• 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.

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