Protein Domain : Aconitase B, HEAT-like domain superfamily IPR036288

Type	Homologous_superfamily
Description	Aconitase (aconitate hydratase; ) 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 [ , ]. 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 small 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) [].This entry represents the N-terminal HEAT-like domain superfamily, which is present in bacterial aconitase (AcnB), but not in AcnA or eukaryotic cAcn/IRP2 or mAcn. This domain consists of 10 alpha helices, forming two curved layers in a right-handed α-α superhelix. The first and last alpha helix interact with another domain within aconitate B, while the middle 8 form a structure made up of four repeating units. This HEAT-like domain is also referred to as domain 5. The helices from domain 5 pack against domain 4 to form a funnel-like structure towards the active site, implicating domain 5 in protein-protein interactions. The HEAT-like domain and the 'swivel' domain that follows it were shown to be sufficient for dimerisation and for AcnB binding to mRNA. An iron-mediated dimerisation mechanism may be responsible for switching AcnB between its catalytic and regulatory roles, as dimerisation requires iron while mRNA binding is inhibited by iron.
Short Name	Aconitase_B_HEAT-like_dom_sf