InterPro domain: IPR033941

3-isopropylmalate dehydratase (or isopropylmalate isomerase; 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 [ 1 ]. 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 [ 2 , 3 ]. LeuC does not bind an iron-sulphur cluster. It is thought that some prokaryotic isopropylamalate dehydrogenases can also function as homoaconitase 4.2.1.36 , converting cis-homoaconitate to homoisocitric acid in lysine biosynthesis [ 4 ]. Homoaconitase has been identified in higher fungi (mitochondria) and several archaea and one thermophilic species of bacteria, Thermus thermophilus [ 5 ]. It is also found in the higher plant Arabidopsis thaliana, where it is targeted to the chloroplast [ 6 ].

This entry represents the aconitase-like catalytic domain of 3-isopropylmalate dehydratase (IPMI) and related uncharacterized proteins.

1. The aconitase family: three structural variations on a common theme. Trends Biochem. Sci. 22, 3-6
2. Branched-chain amino acid biosynthesis genes in Lactococcus lactis subsp. lactis. J. Bacteriol. 174, 6580-9
3. The organization of the leuC, leuD and leuB genes of the extreme thermophile Thermus thermophilus. Gene 222, 125-32
4. Crystal structure of the Pyrococcus horikoshii isopropylmalate isomerase small subunit provides insight into the dual substrate specificity of the enzyme. J. Mol. Biol. 344, 325-33
5. Kinetics and product analysis of the reaction catalysed by recombinant homoaconitase from Thermus thermophilus. Biochem. J. 396, 479-85
6. Functional specification of Arabidopsis isopropylmalate isomerases in glucosinolate and leucine biosynthesis. Plant Cell Physiol. 51, 1480-7