InterPro domain: IPR044137

Aconitase (aconitate hydratase; 4.2.1.3 ) is an iron-sulphur protein that contains a [4Fe-4S]-cluster and catalyses the interconversion of isocitrate and citrate via a cis-aconitate intermediate. Aconitase functions in both the TCA and glyoxylate cycles, however unlike the majority of iron-sulphur proteins that function as electron carriers, the [4Fe-4S]-cluster of aconitase reacts directly with an enzyme substrate. In eukaryotes there is a cytosolic form (cAcn) and a mitochondrial form (mAcn) of the enzyme. In bacteria there are also 2 forms, aconitase A (AcnA) and B (AcnB). Several aconitases are known to be multi-functional enzymes with a second non-catalytic, but essential function that arises when the cellular environment changes, such as when iron levels drop [ 1 , 2 ]. Eukaryotic cAcn and mAcn, and bacterial AcnA have the same domain organisation, consisting of three N-terminal alpha/beta/alpha domains, a linker region, followed by a C-terminal 'swivel' domain with a beta/beta/alpha structure (1-2-3-linker-4), although mAcn is smaller than cAcn. However, bacterial AcnB has a different organisation: it contains an N-terminal HEAT-like domain, followed by the 'swivel' domain, then the three alpha/beta/alpha domains (HEAT-4-1-2-3) [ 3 ].

This entry represents the swivel domain found in Aconitase A and related proteins. This domain is believed to undergo swivelling conformational change in the enzyme mechanism [ 4 ].

1. Moonlighting proteins. Trends Biochem. Sci. 24, 8-11
2. Single-gene disorders: what role could moonlighting enzymes play? Am. J. Hum. Genet. 76, 911-24
3. The aconitase family: three structural variations on a common theme. Trends Biochem. Sci. 22, 3-6
4. Filling a gap in the central metabolism of archaea: prediction of a novel aconitase by comparative-genomic analysis. FEMS Microbiol. Lett. 227, 17-23