Iron -siderophore complexes ferrichromes

For the ferric siderophore complexes, comparison of the CD spectra of the chromium complexes of ferrichrome and enterobactin with the CD spectra of their iron complexes [and the separation of optical isomers of even ferric(benzhydroxamate)3 complexes in nonaqueous solution 192)] have shown that the same rule applied to the CD spectra for chromium complexes can be used for iron siderophore complexes as well iron(III) complexes will have a predominant A configuration in solution if the CD band in... 

Ferrichrome was the first siderophore to be isolated and characterized from the fungi Ustilago sphaerogena in 1952. It is a cyclic hexapeptide with the sequence cycto[(Gly)3-(Al -acetyl-Af -hydroxy-L-ornithine)3] (1) . The biologically active ferrichromes form iron(ni) complexes with a left-handed A-cis helical twist. 

The stability constants of the FeIU siderophore complexes are some of the largest known, e.g. the ferrichrome and ferrioxamine E complexes have log values of the order 29 and 32 respectively as compared to a value of 25 for Fe(edta). So strong are these complexes that microbes have been observed to leach iron from stainless steel vessels. Not surprisingly the siderophores also find use in treating cases of iron poisoning and for the elimination of iron from cases of thalassaemia.84 Complexation of Fe11 is considerably weaker than that of FeIU and this is probably utilized for the release of the iron within the cells. 

Escherichia coli has at least five independent transport systems, one of which is the low affinity pathway described above. In addition, it synthesizes enterobactin as a siderophore it can take up the iron(III) complex of ferrichrome, a siderophore synthesized by certain fungi there is a citrate-induced system, and a less common process involving aerobactin. 

In times of iron deficiency, many bacteria and fungi release low molecular weight chelators called siderophores (see Iron Transport Siderophores). These molecules bind ferric iron tightly and the ferric-siderophore complexes are then transported into the cell by a system of uptake proteins. The first stage in the uptake process involves an outer membrane receptor specific to each siderophore. One of the best characterized of these receptors is FhuA, the ferrichrome uptake receptor of E. coli, and we will describe this in detail. However, though other ferric-siderophore complexes are taken up by cells, and their iron released by systems similar to those of ferrichrome, their mechanisms may vary from those of ferrichrome in some respects. FepA and FecA" are two of the outer membrane ferric-siderophore receptors that have recently been structurally characterized. 

The crystal structure of FhuA bound to the iron ligand ferrichrome has also been determined. This shows that the ferric-siderophore complex binds inside the barrel above the plug, forming hydrogen bonds and van der Waals interactions with residues within the plug domain and with the /3-strands of the barrel (Figure 2). 

FhuD delivers the ferric-siderophore complex to the FhuBC complex in the cytoplasmic membrane. FhuB is an intrinsic cytoplasmic membrane protein through which the iron complex can pass, driven by energy supplied by ATP hydrolysis catalyzed by the ATPase FhuC. Ferrous iron may be released from the hydroxamate via reduction by the reductase FhuF, which is loosely associated with the cytoplasmic membrane and, like FhuD, appears to have a lower specificity than FhuA and is active with coprogen and ferrichrome. ... 

Figure 3.2 Chemical structures of selected siderophores to demonstrate the four major structural classes and the different solutions of microorganisms to scavenge iron. See for comparison the conformations of the Fe3+-complexes of ferrichrome and albomycin shown in Figure 3.5.

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