Homoaconitase/3-isopropylmalate dehydratase, large subunit, prokaryotic <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 (LeuC), as well as homoaconitase enzymes, from prokaryotes. Homoaconitase, aconitase and 3-isopropylmalate dehydratase have similar overall structures and domain organisation [<cite idref="PUB00005471"/>]. All are dehydratases that bind a [4Fe-4S]-cluster.</p><p>Information about related proteins can be found at Protein of the Month: Aconitase [<cite idref="PUB00036022"/>].</p>