Aconitase

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Aconitase (ACO) is an enzymatic domain that confers the ability to catalyse the equilibrium

citrate = aconitate + H2O = isocitrate

This reaction is part of the citrate (TCA-, Krebs-)cycle.

In most organims, there is a cytosolic enzyme with an ACO domain (cAc), and in eukaryotes, a second copy of it was introduced with mitochondria (mAc). Plants developed even more copies in mitochondria.

Drag the structure with the mouse to rotate
A specialty of cAc is that in mammals it has developed a second function as inhibitor of those mRNA that carry an iron-regulatory element (IRE). Therefore, the cytosolic cAc is named IREBP for IRE-binding protein when this function is talked about. Only one of the two functions is active, depending on whether the (4Fe4S) cofactor is present in the molecule: it's essential for the ACO function. You can see, by looking at the morph, how much the enzyme structure differs between those two functions.

Available structures

In the PDB, nearly all deposited structures are from mammals, 1l5j is from E.coli. Also, only 2ipy shows the IREBP function of cAc---it's also the only from rabbit. There are only two other cAc structures, with and without citrate, also the only from human. All other structures are either cow or pig, and a mutant from pig; all three proteins with several different ligands and inhibitors.

  • 1aco - mAc (Bos taurus) with trans-aconitate (inhibitor)
  • 1ami - mAc (Bos taurus) with methylisocitrate
  • 1amj - mAc (Bos taurus) with sulfate and hydroxide
  • 1b0j - S642 mutant of mAc (Sus scrofa) with isocitrate (substrate)
  • 1b0k - S642 mutant of mAc (Sus scrofa) with fluorocitrate (inhibitor)
  • 1b0m - S642 mutant of mAc (Sus scrofa) with fluorocitrate (inhibitor) and oxygen
  • 1c96 - S642 mutant of mAc (Sus scrofa) with citrate
  • 1c97 - S642 mutant of mAc (Sus scrofa) with isocitrate and oxygen
  • 1fgh - mAc (Bos taurus) with 4-hydroxy-trans-aconitate (inhibitor)
  • 1l5j - aconitase B (E. coli) with Fe3S4 and aconitate
  • 1nis - mAc (Bos taurus) with nitrocitrate (inhibitor)
  • 1nit - mAc (Bos taurus) with sulfate
  • 2b3x - cAc (human) as aconitase with Fe4S4
  • 2b3y - cAc (human) as aconitase with Fe4S4 and citrate
  • 2ipy - cAc (Oryctolagus cuniculus) as IRP1 with ferritin RNA
  • 5acn - mAc (Sus scrofa) with Fe3S4 (missing a Fe)
  • 6acn - mAc (Sus scrofa) with Fe4S4
  • 7acn - mAc (Sus scrofa) with isocitrate
  • 8acn - mAc (Sus scrofa) with nitroisocitrate

Weblinks

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