Aconitase, iron-sulfur domain
Short name | Aconitase_4Fe-4S_dom |
Overlapping entries |
Description
* 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)
* 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
* 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 coli and Salmonella enterica
References
1.The role of iron regulatory proteins in mammalian iron homeostasis and disease. Rouault TA. Nat. Chem. Biol. 2, 406-14, (2006). View articlePMID: 16850017
2.Switching aconitase B between catalytic and regulatory modes involves iron-dependent dimer formation. Tang Y, Guest JR, Artymiuk PJ, Green J. Mol. Microbiol. 56, 1149-58, (2005). View articlePMID: 15882410
3.Evolution of the iron-responsive element. Piccinelli P, Samuelsson T. RNA 13, 952-66, (2007). View articlePMID: 17513696
4.Single-gene disorders: what role could moonlighting enzymes play? Sriram G, Martinez JA, McCabe ER, Liao JC, Dipple KM. Am. J. Hum. Genet. 76, 911-24, (2005). View articlePMID: 15877277
5.Moonlighting proteins. Jeffery CJ. Trends Biochem. Sci. 24, 8-11, (1999). View articlePMID: 10087914
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
7.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
8.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
9.Cell biology. "Pumping" iron: the proteins. Beutler E. Science 306, 2051-3, (2004). View articlePMID: 15604397
10.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
11.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
12.Crystal structure of human iron regulatory protein 1 as cytosolic aconitase. Dupuy J, Volbeda A, Carpentier P, Darnault C, Moulis JM, Fontecilla-Camps JC. Structure 14, 129-39, (2006). View articlePMID: 16407072
13.Structure of dual function iron regulatory protein 1 complexed with ferritin IRE-RNA. Walden WE, Selezneva AI, Dupuy J, Volbeda A, Fontecilla-Camps JC, Theil EC, Volz K. Science 314, 1903-8, (2006). View articlePMID: 17185597
14.Post-transcriptional regulation of bacterial motility by aconitase proteins. Tang Y, Guest JR, Artymiuk PJ, Read RC, Green J. Mol. Microbiol. 51, 1817-26, (2004). View articlePMID: 15009904
15.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
Cross References
Contributing Member Database Entry
- SUPERFAMILY:SSF53732