Aconitase: Difference between revisions
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'''Aconitase (ACO)''' is an enzymatic domain that confers the ability to catalyse the equilibrium | '''Aconitase (ACO)''' is an enzymatic domain that confers the ability to catalyse the equilibrium | ||
:citrate = aconitate + H<sub>2</sub>O = isocitrate | :citrate = aconitate + H<sub>2</sub>O = L-isocitrate | ||
This reaction is part of the citrate (TCA-, Krebs-)cycle. | 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. | 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. | ||
<applet load='Morph_2ipy-2b3x.pdb.gz' scene='Aconitase/2ipy-total/2' size='400' frame='true' align='right' caption="" />A specialty of cAc is that in mammals it has developed a <scene name='Aconitase/2ipy-total/2'>second function</scene> as inhibitor of <scene name='Aconitase/2ipy-rna/1'>those mRNA</scene> that carry an <scene name='Aconitase/2ipy-rna-ire/1'>iron- | == Catalytic mechanism of mitochondrial ACO == | ||
<applet load=7acn scene='Aconitase/7acn-sf4/1' size='400' frame='true' align='left' caption="Mitochondrial aconitase from pig, PDB [[7acn]]." />The bulk of citrate cycle processing happens in mitochondria and so, studies concentrated on the mitochondrial ACO. The <scene name='Aconitase/7acn-sf4-3cys/1'>(4Fe-4S) cofactor is held in place</scene> by three sulfur atoms belonging to the cysteins-385, -448, and -451. | |||
<!--It is clear that, in order to synthesize L-isocitrate, stereoselective catalysis must occur.--> | |||
== Cytosolic aconitase and its other function == | |||
<applet load='Morph_2ipy-2b3x.pdb.gz' scene='Aconitase/2ipy-total/2' size='400' frame='true' align='right' caption="Cytosolic aconitase from rabbit (bound to RNA) and human (with Fe4S4 cluster), from PDB [[2ipy]] and [[2b3x]]." />A specialty of cAc is that in mammals it has developed a <scene name='Aconitase/2ipy-total/2'>second function</scene> as inhibitor of <scene name='Aconitase/2ipy-rna/1'>those mRNA</scene> that carry an <scene name='Aconitase/2ipy-rna-ire/1'>iron-responsive element (IRE)</scene>. 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 <scene name='Aconitase/2b3x-cluster/1'>the (4Fe-4S) cofactor</scene> is present in the molecule: it's essential for <scene name='Aconitase/2b3x-total/1'>the ACO function</scene>. You can see, by <scene name='Aconitase/Morph/2'>looking at the morph</scene>, how much the enzyme structure differs between those two functions. | |||
<!--== Available structures == | <!--== Available structures == | ||
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*[[2ipy]] - cAc (''Oryctolagus cuniculus'') as IRP1 with ferritin RNA | *[[2ipy]] - cAc (''Oryctolagus cuniculus'') as IRP1 with ferritin RNA | ||
*[[5acn]] - mAc (''Sus scrofa'') with Fe3S4 (missing a Fe) | *[[5acn]] - mAc (''Sus scrofa'') with Fe3S4 (missing a Fe) | ||
*[[6acn]] - mAc (''Sus scrofa'') with | *[[6acn]] - mAc (''Sus scrofa'') with tricarballylic acid | ||
*[[7acn]] - mAc (''Sus scrofa'') with isocitrate | *[[7acn]] - mAc (''Sus scrofa'') with isocitrate | ||
*[[8acn]] - mAc (''Sus scrofa'') with nitroisocitrate | *[[8acn]] - mAc (''Sus scrofa'') with nitroisocitrate | ||
Revision as of 16:34, 18 February 2009
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
|
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
|
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.
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Anthony Noles, Ralf Stephan, Alexander Berchansky, David Canner, Eran Hodis, Angel Herraez, Jaime Prilusky, Michal Harel, Joel L. Sussman
