Aconitase

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

citrate = aconitate + H₂O = L-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.

Catalytic mechanism of mitochondrial ACO

spinqualitylabelsall models Mitochondrial aconitase from pig, PDB 7acn. Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D

The bulk of citrate cycle processing happens in mitochondria and so, studies concentrated on the mitochondrial ACO. The (4Fe-4S) cofactor is held in place by three sulfur atoms belonging to the cysteins-385, -448, and -451.

Cytosolic aconitase and its other function

spinqualitylabelsall models Cytosolic aconitase from rabbit (bound to RNA) and human (with Fe4S4 cluster), from PDB 2ipy and 2b3x. Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D

A specialty of cAc is that in mammals it has developed a second function as inhibitor of those mRNA that carry an iron-responsive 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 (4Fe-4S) 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.

Weblinks

• Molecule of the Month: Aconitase and Iron Regulatory Protein 1
• Aconitase at Wikipedia

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