Aconitase/Iron-responsive element-binding protein 2
Short name | Aconitase/IRP2 |
Overlapping homologous superfamilies | |
family relationships |
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
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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
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5.Moonlighting proteins. Jeffery CJ. Trends Biochem. Sci. 24, 8-11, (1999). View articlePMID: 10087914
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7.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
8.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
9.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
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11.The phosphinomethylmalate isomerase gene pmi, encoding an aconitase-like enzyme, is involved in the synthesis of phosphinothricin tripeptide in Streptomyces viridochromogenes. Heinzelmann E, Kienzlen G, Kaspar S, Recktenwald J, Wohlleben W, Schwartz D. Appl Environ Microbiol 67, 3603-9, (2001). View articlePMID: 11472937
12.The bifunctional iron-responsive element binding protein/cytosolic aconitase: the role of active-site residues in ligand binding and regulation. Philpott CC, Klausner RD, Rouault TA. Proc. Natl. Acad. Sci. U.S.A. 91, 7321-5, (1994). View articlePMID: 8041788
13.Molecular characterization of a second iron-responsive element binding protein, iron regulatory protein 2. Structure, function, and post-translational regulation. Samaniego F, Chin J, Iwai K, Rouault TA, Klausner RD. J. Biol. Chem. 269, 30904-10, (1994). PMID: 7983023
14.First Biochemical Characterization of a Methylcitric Acid Cycle from Bacillus subtilis Strain 168. Reddick JJ, Sirkisoon S, Dahal RA, Hardesty G, Hage NE, Booth WT, Quattlebaum AL, Mills SN, Meadows VG, Adams SLH, Doyle JS, Kiel BE. Biochemistry 56, 5698-5711, (2017). View articlePMID: 28956599
Cross References
ENZYME
Genome Properties