Siderophore models

The spectra shown in Fig. 16 have been used to probe the bonding in high-spin Fe(III) complexes related to the siderophores. The L-edge spectra of three siderophore model compounds [Fe(ox)3]3, [Fe(cat)3]3, [Fe(aha)3], and the... 

IRON SEQUESTRATION BY SMALL MOLECULES THERMODYNAMIC AND KINETIC STUDIES OF NATURAL SIDEROPHORES AND SYNTHETIC MODEL COMPOUNDS... 

While studying the formation kinetics of complexes gives useful mechanistic information about the reactivity of the iron center when bound to a particular siderophore, it is not necessarily a good model for how environmental iron will react in the siderophore system of interest. In biological systems,... 

A series of model siderophore molecular recognition studies coupled with host-guest carrier facilitated model membrane transport studies was reported (198-202). Three approaches were taken which incorporate (i) second coordination shell host-guest complexation, (ii) ternary complex formation, and (iii) a combination of ternary complex - second coordination shell host-guest complex formation. Examples of these approaches are described below. 

Fe(III) displacement of Al(III), Ga(III), or In(III) from their respective complexes with these tripodal ligands, have been determined. The M(III)-by-Fe(III) displacement processes are controlled by the ease of dissociation of Al(III), Ga(III), or In(III) Fe(III) may in turn be displaced from these complexes by edta (removal from the two non-equivalent sites gives rise to an appropriate kinetic pattern) (343). Kinetics and mechanism of a catalytic chloride ion effect on the dissociation of model siderophore-hydroxamate iron(III) complexes chloride and, to lesser extents, bromide and nitrate, catalyze ligand dissociation through transient coordination of the added anion to the iron (344). A catechol derivative of desferrioxamine has been found to remove iron from transferrin about 100 times faster than desferrioxamine itself it forms a significantly more stable product with Fe3+ (345). 

Due to the usual diversity of components in the medium, there will be a need to consider that the species taken up interacts with other species while diffusing towards the organism surface (see Figure 19). In some cases (as in the aquatic prokaryotes that exudate Fe chelators called siderophores to improve the availability of Fe see Chapter 9 in this volume), the medium is modified on purpose by the organisms [11,47-49], A simple model for this interaction assumes the complexation of M with a ligand, with elementary interconversion kinetics between the free and complexed forms ... 

In any case, exceptions to the FIAM have been pointed out [2,11,38,44,74,76,78]. For example, the uptake has been shown to depend on the Cj M or rMI (e.g. in the case of siderophores [11] or hydrophobic complexes [43,50]), rather than on the free c M. Several authors [11,12,15] showed that a scheme taking into account the kinetics of parallel transfer of M from several solution complexes to the internalisation transporter ( ligand exchange ) can lead to exceptions to the FIAM, even if there is no diffusion limitation. Adsorption equilibrium has been assumed in all the models discussed so far in this chapter, and the consideration of adsorption kinetics is kept for Section 4. Within the framework of the usual hypotheses in this Section 3, we would expect that the FIAM is less likely to apply for larger radii and smaller diffusion coefficients (perhaps arising from D due to the labile complexation of M with a large macromolecule or a colloid particle, see Section 3.3). 

In principle, any kind of limitation of the medium (e.g. due to some kind of clustering in a zone) tends to diminish the individual uptake rate [31]. From the point of view of modelling, the breaking of the symmetry rapidly complicates the problem (see Chapter 3 in this volume). As an exception to the general rule of decreased uptake due to inter-cell competition, it has been shown [49] that biouptake through siderophore excretion is only viable for nonisolated cells. 

ABC transporters involved in the uptake of siderophores, haem, and vitamin B]2 are widely conserved in bacteria and Archaea (see Figure 10). Very few species lack representatives of the siderophore family transporters. These species are mainly intracellular parasites whose metabolism is closely coupled to the metabolism of their hosts (e.g. mycoplasma), or bacteria with no need for iron (e.g. lactobacilli). In many cases, several systems of this transporter family can be detected in a single species, thus allowing the use of structurally different chelators. Most systems were exclusively identified by sequence data analysis, some were biochemically characterised, and their substrate specificity was determined. However, only very few systems have been studied in detail. At present, the best-characterised ABC transporters of this type are the fhuBCD and the btuCDF systems of E. coli, which might serve as model systems of the siderophore family. Therefore, in the following sections, this report will mainly focus on the components that mediate ferric hydroxamate uptake (fhu) and vitamin B12 uptake (htu). 

Staphyloferrin B (59, Fig. 17) is produced together with staphyloferrin A (see below Sect. 4.4) by Staphylococcus hyicus and other staphylococci 94, 131), by Ralstonia eutropha 250) (= Cupriavidus metallidurans 90a)). Comparison of its CD spectrum with those of model compounds suggests the (S)-configuration of the central citric acid C-atom. Mass spectral investigations show a 1 1 Fe V to-ligand ratio, and NMR studies of the Ga " complex confirm the participation of the two ot-hydroxy- and of the a-amino acid functions in complex formation. Uptake studies with Fe " showed that staphyloferrin B acts as a siderophore, but it is less efficient than staphyloferrin A. 

Fadeev E, Luo M, Groves JT (2005) Synthesis and Structural Modeling of the Amphiphilic Siderophore Rhizobactin-1021 and its Analogs. Bioorg Med Chem Lett 15 3771... 

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