Protein Domain : IPR015932

Type:  Domain Name:  Aconitase/3-isopropylmalate dehydratase large subunit, alpha/beta/alpha, subdomain 2
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) []. Below is a description of some of the multi-functional activities associated with different aconitases.Eukaryotic mAcn catalyses the second step of the mitochondrial TCA cycle, which is important for energy production, providing high energy electrons in the form of NADH and FADH2 to the mitochondrial oxidative phosphorylation pathway []. The TCA cycle also provides precursors for haem and amino acid production. This enzyme has a second, non-catalytic but essential role in mitochondrial DNA (mtDNA) maintenance: mAcn acts to stabilise mtDNA, forming part of mtDNA protein-DNA complexes known as nucleoids. mAcn is thought to reversibly model nucleoids to directly influence mitochondrial gene expression in response to changes in the cellular environment. Therefore, mAcn can influence the expression of components of the oxidative phosphorylation pathway encoded in mtDNA. Eukaryotic cAcn enzyme balances the amount of citrate and isocitrate in the cytoplasm, which in turn creates a balance between the amount of NADPH generated from isocitrate by isocitrate dehydrogenase with the amount of acetyl-CoA generated from citrate by citrate lyase. Fatty acid synthesis requires both NADPH and acetyl-CoA, as do other metabolic processes, including the need for NADPH to combat oxidative stress. The enzymatic form of cAcn predominates when iron levels are normal, but if they drop sufficiently to cause the disassembly of the [4Fe-4S]-cluster, then cAcn undergoes a conformational change from a compact enzyme to a more open L-shaped protein known as iron regulatory protein 1 (IRP1; or IRE-binding protein 1, IREBP1) [, ]. As IRP1, the catalytic site and the [4Fe-4S]-cluster are lost, and two new RNA-binding sites appear. IRP1 functions in the post-transcriptional regulation of genes involved in iron metabolism - it binds to mRNA iron-responsive elements (IRE), 30-nucleotide stem-loop structures at the 3' or 5' end of specific transcripts. Transcripts containing an IRE include ferritin L and H subunits (iron storage), transferrin (iron plasma chaperone), transferrin receptor (iron uptake into cells), ferroportin (iron exporter), mAcn, succinate dehydrogenase, erythroid aminolevulinic acid synthetase (tetrapyrrole biosynthesis), among others. If the IRE is in the 5'-UTR of the transcript (e.g. in ferritin mRNA), then IRP1-binding prevents its translation by blocking the transcript from binding to the ribosome. If the IRE is in the 3'-UTR of the transcript (e.g. transferrin receptor), then IRP1-binding protects it from endonuclease degradation, thereby prolonging the half-life of the transcript and enabling it to be translated [].IRP2 is another IRE-binding protein that binds to the same transcripts as IRP1. However, since IRP1 is predominantly in the enzymatic cAcn form, it is IRP2 that acts as the major metabolic regulator that maintains iron homeostasis []. Although IRP2 is homologous to IRP1, IRP2 lacks aconitase activity, and is known only to have a single function in the post-transcriptional regulation of iron metabolism genes []. In iron-replete cells, IRP2 activity is regulated primarily by iron-dependent degradation through the ubiquitin-proteasomal system.Bacterial AcnB is also known to be multi-functional. In addition to its role in the TCA cycle, AcnB was shown to be a post-transcriptional regulator of gene expression in Escherichia coliand Salmonella enterica[, ]. In S. enterica, AcnB initiates a regulatory cascade controlling flagella biosynthesis through an interaction with the ftsH transcript, an alternative RNA polymerase sigma factor. This binding lowers the intracellular concentration of FtsH protease, which in turn enhances the amount of RNA polymerase sigma32 factor (normally degraded by FtsH protease), and sigma32 then increases the synthesis of chaperone DnaK, which in turn promotes the synthesis of the flagellar protein FliC. AcnB regulates the synthesis of other proteins as well, such as superoxide dismutase (SodA) and other enzymes involved in oxidative stress.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[]. This entry represents a domain with an alpha/beta/alpha topology. This structural domain usually occurs in triplicate, with domains 1 and 3 being the most closely related since they share the same pseudo 2-fold symmetry. This entry represents domain 2. This triple domain region is found at the N-terminal of eukaryotic mAcn, cAcn/IPR1 and IRP2, and bacterial AcnA, but in the C-terminal of bacterial AcnB; in each case, this region binds the [4Fe-4S]-cluster. This triple domain region is also found in the large subunit of isopropylmalate dehydratase (LeuC). Short Name:  Aconitase/IPMdHydase_lsu_aba_2
Paste the following link

0 Child Features

0 Contains

1 Cross References

Identifier
G3DSA:3.40.1060.10

14 Found Ins

DB identifier Type Name
IPR001030 Domain Aconitase/3-isopropylmalate dehydratase large subunit, alpha/beta/alpha domain
IPR015937 Family Aconitase/isopropylmalate dehydratase
IPR006249 Family Aconitate/Iron-responsive element-binding protein 2
IPR006251 Family Homoaconitase/3-isopropylmalate dehydratase, large subunit
IPR006248 Family Aconitase, mitochondrial-like
IPR004430 Family 3-isopropylmalate dehydratase, large subunit
IPR004406 Family Aconitase B
IPR015934 Family Aconitase/2-methylisocitrate dehydratase
IPR012708 Family 2-methylisocitrate dehydratase AcnD, Fe/S-dependent
IPR004418 Family Homoaconitase, mitochondrial
IPR012235 Family 3-isopropylmalate dehydratase, fused small/large subunit
IPR006250 Family Aconitase, putative
IPR011823 Family 3-isopropylmalate dehydratase, large subunit, bacteria
IPR011826 Family Homoaconitase/3-isopropylmalate dehydratase, large subunit, prokaryotic

1 GO Annotation

GO Term Gene Name
GO:0008152 IPR015932

1 Ontology Annotations

GO Term Gene Name
GO:0008152 IPR015932

0 Parent Features

3256 Proteins

DB identifier UniProt Accession Secondary Identifier Organism Name Length
Cucsa.179920.2 A0A0A0KXG6 PAC:16967244 Cucumis sativus 249  
Cucsa.179920.3 PAC:16967245 Cucumis sativus 193  
Cucsa.179920.1 A0A0A0KXG6 PAC:16967243 Cucumis sativus 249  
Cucsa.236980.1 A0A0A0KXX5 PAC:16970524 Cucumis sativus 277  
orange1.1g019862m A0A067DNL3 PAC:18110776 Citrus sinensis 334  
orange1.1g022394m A0A067ECZ1 PAC:18121000 Citrus sinensis 298  
orange1.1g024098m A0A067E983 PAC:18121001 Citrus sinensis 272  
Ciclev10021386m V4TY96 PAC:20806427 Citrus clementina 298  
Gorai.001G144200.1 A0A0D2PQN0 PAC:26821469 Gossypium raimondii 137  
32301 I0Z8C6 PAC:27393401 Coccomyxa subellipsoidea C-169 171  
104069 C1EGX5 PAC:27403812 Micromonas sp RCC299 392  
Glyma.11G165500.2.p A0A0R0HID2 PAC:30531569 Glycine max 79  
Brara.F01225.1.p A0A397Z3I9 PAC:30629709 Brassica rapa FPsc 299  
Brara.J00775.1.p A0A397XRX1 PAC:30612304 Brassica rapa FPsc 658  
Bostr.26527s0157.1.p PAC:30654244 Boechera stricta 90  
Cre16.g658300.t3.1 A0A2K3CTC3 PAC:30777443 Chlamydomonas reinhardtii 904  
Cre16.g658300.t1.1 A0A2K3CTC7 PAC:30777441 Chlamydomonas reinhardtii 906  
Cre16.g658300.t2.1 A0A2K3CTC4 PAC:30777442 Chlamydomonas reinhardtii 906  
Cre07.g320350.t1.2 A0A2K3DJ03 PAC:30774643 Chlamydomonas reinhardtii 319  
Spipo4G0077900 PAC:31504600 Spirodela polyrhiza 287  
evm_27.model.AmTr_v1.0_scaffold00098.15 W1NW44 PAC:31562115 Amborella trichopoda 105  
Traes_1DL_D897AAEB0.1 PAC:31825881 Triticum aestivum 61  
Traes_3AS_42F2D9445.3 PAC:31811215 Triticum aestivum 253  
Traes_3AS_42F2D9445.2 PAC:31811213 Triticum aestivum 367  
Traes_3AS_42F2D9445.1 PAC:31811214 Triticum aestivum 364  
Traes_3B_B6A0537FA.16 PAC:32020357 Triticum aestivum 173  
Traes_3B_B6A0537FA.12 PAC:32020353 Triticum aestivum 445  
Traes_3DS_0A1F1EDD5.9 PAC:31958029 Triticum aestivum 274  
Traes_3DS_0A1F1EDD5.8 PAC:31958028 Triticum aestivum 287  
Traes_3DS_0A1F1EDD5.11 PAC:31958031 Triticum aestivum 187  

15 Publications

First Author Title Year Journal Volume Pages PubMed ID
            9020582
            10087914
            15877277
            9813279
            15522288
            1400210
            16850017
            17513696
            15882410
            15009904
            15543948
            15604397
            16524361
            16407072
            17185597