Aconitase (aconitate hydratase) (EC 4.2.1.3) [1] is the enzyme from the tricarboxylic acid cycle that catalyzes the reversible isomerization of citrate and isocitrate. Cis-aconitate is formed as an intermediary product during the course of the reaction. In eukaryotes two isozymes of aconitase are known to exist: one found in the mitochondrial matrix and the other found in the cytoplasm. Aconitase, in its active form, contains a 4Fe-4S iron-sulfur cluster; three cysteine residues have been shown to be ligands of the 4Fe-4S cluster.

It has been shown that the aconitase family also contains the following proteins:

• Iron-responsive element binding protein (IRE-BP). IRE-BP is a cytosolic protein that binds to iron-responsive elements (IREs). IREs are stem-loop structures found in the 5'UTR of ferritin, and delta aminolevulinic acid synthase mRNAs, and in the 3'UTR of transferrin receptor mRNA. IRE-BP also express aconitase activity.
• 3-isopropylmalate dehydratase (EC 4.2.1.33) (isopropylmalate isomerase), the enzyme that catalyzes the second step in the biosynthesis of leucine.
• Homoaconitase (EC 4.2.1.36) (homoaconitate hydratase), an enzyme that participates in the α-aminoadipate pathway of lysine biosynthesis and that converts cis-homoaconitate into homoisocitric acid.
• Esherichia coli protein ybhJ.

As a signature for proteins from the aconitase family we have selected two conserved regions that contain the three cysteine ligands of the 4Fe-4S cluster.