| Description | 3-isopropylmalate dehydratase (or isopropylmalate isomerase; ) 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 [ ]. 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 [ , ]. LeuC does not bind an iron-sulphur cluster. It is thought that some prokaryotic isopropylamalate dehydrogenases can also function as homoaconitase , converting cis-homoaconitate to homoisocitric acid in lysine biosynthesis [ ]. Homoaconitase has been identified in higher fungi (mitochondria) and several archaea and one thermophilic species of bacteria, Thermus thermophilus []. It is also found in the higher plant Arabidopsis thaliana, where it is targeted to the chloroplast [].This entry represents the large subunit of 3-isopropylmalate dehydratase (LeuC), as well as homoaconitase, certain aconitases and uncharacterised proteins. Homoaconitase, aconitase and 3-isopropylmalate dehydratase have similar overall structures and domain organisation [ ]. All are dehydratases that bind a [4Fe-4S]-cluster. The majority of the members of this family have been designated as 3-isopropylmalate dehydratase large subunit (LeuC) in microbial genome annotation, but the only characterised member is Thermus thermophilus homoaconitase, an enzyme of a non-aspartate pathway of lysine biosynthesis. | Name | Homoaconitase/3-isopropylmalate dehydratase, large subunit |
| Short Name | Homoacnase/IPMdehydase_lsu | Type | Family |
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