<p>3-isopropylmalate dehydratase (or isopropylmalate isomerase; <db_xref db="EC" dbkey="4.2.1.33"/>) catalyses the stereo-specific isomerisation of 2-isopropylmalate and 3-isopropylmalate, via the formation of 2-isopropylmaleate. This enzyme performs the second step in the biosynthesis of leucine, and is present in most prokaryotes and many fungal species. The prokaryotic enzyme is a heterodimer composed of a large (LeuC) and small (LeuD) subunit, while the fungal form is a monomeric enzyme. Both forms of isopropylmalate are related and are part of the larger aconitase family [<cite idref="PUB00005471"/>]. Aconitases are mostly monomeric proteins which share four domains in common and contain a single, labile [4Fe-4S] cluster. Three structural domains (1, 2 and 3) are tightly packed around the iron-sulphur cluster, while a fourth domain (4) forms a deep active-site cleft. The prokaryotic enzyme is encoded by two adjacent genes, leuC and leuD, corresponding to aconitase domains 1-3 and 4 respectively [<cite idref="PUB00033924"/>, <cite idref="PUB00016210"/>]. LeuC does not bind an iron-sulphur cluster. It is thought that some prokaryotic isopropylamalate dehydrogenases can also function as homoaconitase <db_xref db="EC" dbkey="4.2.1.36"/>, converting cis-homoaconitate to homoisocitric acid in lysine biosynthesis [<cite idref="PUB00032014"/>]. Homoaconitase has been identified in higher fungi (mitochondria) and several archaea and one thermophilic species of bacteria, <taxon tax_id="274">Thermus thermophilus</taxon> [<cite idref="PUB00036023"/>]. </p> <p>This entry represents the large subunit of 3-isopropylmalate dehydratase, or the large subunit domain of single-chain forms of this enzyme. Homoaconitase, aconitase, and 3-isopropylmalate dehydratase have similar overall structures. All are dehydratases (<db_xref db="EC" dbkey="4.2.1"/>) and bind a [4Fe-4S]-cluster. 3-isopropylmalate dehydratase is split into large (leuC) and small (leuD) chains in eubacteria. Several pairs of archaeal proteins resemble the leuC and leuD pair in length and sequence but even more closely resemble the respective domains of homoaconitase, and their identity is uncertain. The archaeal leuC-like proteins are not included in group.</p> 3-isopropylmalate dehydratase, large subunit