F
IPR004430

3-isopropylmalate dehydratase, large subunit

InterPro entry
Short name3-IsopropMal_deHydase_lsu
Overlapping
homologous
superfamilies
 

Description

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 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 (
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.

References

1.The aconitase family: three structural variations on a common theme. Gruer MJ, Artymiuk PJ, Guest JR. Trends Biochem. Sci. 22, 3-6, (1997). View articlePMID: 9020582

2.Branched-chain amino acid biosynthesis genes in Lactococcus lactis subsp. lactis. Godon JJ, Chopin MC, Ehrlich SD. J. Bacteriol. 174, 6580-9, (1992). View articlePMID: 1400210

3.The organization of the leuC, leuD and leuB genes of the extreme thermophile Thermus thermophilus. Tamakoshi M, Yamagishi A, Oshima T. Gene 222, 125-32, (1998). View articlePMID: 9813279

4.Crystal structure of the Pyrococcus horikoshii isopropylmalate isomerase small subunit provides insight into the dual substrate specificity of the enzyme. Yasutake Y, Yao M, Sakai N, Kirita T, Tanaka I. J. Mol. Biol. 344, 325-33, (2004). View articlePMID: 15522288

5.Kinetics and product analysis of the reaction catalysed by recombinant homoaconitase from Thermus thermophilus. Jia Y, Tomita T, Yamauchi K, Nishiyama M, Palmer DR. Biochem. J. 396, 479-85, (2006). View articlePMID: 16524361

6.Functional specification of Arabidopsis isopropylmalate isomerases in glucosinolate and leucine biosynthesis. He Y, Chen B, Pang Q, Strul JM, Chen S. Plant Cell Physiol. 51, 1480-7, (2010). View articlePMID: 20663849

GO terms

Cross References

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