Aconitase iron ligands

Aconitase Iron-responsible binding protein Ligand concentration A in high iron cone, but B in decreased iron cone. 

Fig. 6. A schematic view of the [3Fe-4S] Emd [4Fe-4S] cores, as versatile structures. The absence of one site leads to the formation of a [3Fe-4S] core. The cubane structure can incorporate different metals (in proteins, M = Fe, Co, Zn, Cd, Ni, Tl, Cs), and S, N, O may be coordinating atoms from hgands (Li). The versatihty csm be extended to higher coordination number at the iron site and a water molecule can even be a ligand, exchangeable with substrate (as in the case of aconitase (,87)). The most characteristic binding motifs are schematically indicated, for different situations proteins accommodating [3Fe-4S], [4Fe-4S], [3Fe-4S] + [4Fe-4S], and [4Fe-4S] -I- [4Fe-4S] clusters. A disulfide bridge may replace a cluster site (see text).

Figure 7.8 Regulation of IRP-1 and IRP-2. The two IRPs are shown as homologous four domain proteins that bind to IREs (left) In iron-replete cells, IRP-1 assembles a cubane Fe-S cluster that is liganded via cys-437, -503 and -506. Similar cysteines are conserved in IRP-2 (Cys-512, -578 and -581), but it is unresolved as to whether they also coordinate an Fe-S cluster, (right) In iron-replete cells, IRP-2 is targeted for destruction via a specific region (shaded in black), whereas IRP-1, with a 4Fe-4S cluster, is stable and active as a cytoplasmic aconitase. Multiple signals induce IRE-binding by IRP-1 with distinct kinetics. Whether or not NO and H2O2 induce IRP-1 by apoprotein formation remains to be addressed directly. From Hentze and Kuhn, 1996. Copyright (1996) National Academy of Sciences, USA.

Figure 8-2 Posttranscriptional regulation by IRE/IRP interactions. In iron-replete cells, IRPs do not bind to IREs. Iron starvation induces IRPs to bind to their ligands, resulting in stabilization of transferrin receptor mRNA and translational inhibition of the mRNAs encoding ferritin H- and L-chain), eALAS and mitochondrial aconitase.

Aconitase was initially crystallized in the [3Fe-4S]" " form, and these crystals could be converted to the [4Fe S] " " form by addition of ferrous ammonium sulfate. Alternatively, anaerobic crystallization methods were used to crystallize the [4Fe-4S] " " form directly." The iron-sulfur cluster of aconitase sits within a solvent-filled cleft in the protein structure and is coordinated by Cys 358, Cys 421, and Cys 424. The [3Fe S]+ cluster shows the typically cuboidal geometry, with the open iron site directed toward the active site cleft. Conversion to the active [4Fe-4S] " " form results in almost no structural perturbation, with the extra iron atom simply being inserted into the vacant site in the cluster. The fourth iron is tetrahedrally coordinated, but with a solvent hydroxide rather than a cysteine as the fourth ligand. (The electron density clearly reveals a bound solvent, and previous ENDOR studies had demonstrated that the bound species was associated with only a single proton.)... 

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