Siderophores binding sites

Siderophore binding sites for iron(III) are for the most part negatively charged and therefore, in aqueous solution there is a competition between H+ and Fe3+ binding. Consequently, the equilibrium expression for the formation of the iron-siderophore complex must take into account proton participation in the reaction. 

The implications of these mechanistic studies for our understanding of environmental iron sequestration by siderophores is as follows. The hydroxyl containing aqua ferric ions will tend to form ferri-siderophore complexes more rapidly than the hexaaqua ion and ferrous ion will be sequestered more rapidly than the ferric ion. However, once in a siderophore binding site the ferrous ion will be air oxidized to the ferric ion, due to the negative redox potentials (see Section III.D). This also means that Fe dissolution from rocks will be influenced by mineral composition (other donors in the first coordination shell) as well as surface reductases in contact with the rock, and of course surface area (4,13). 

Using linear regression, it is possible to estimate the protonation constants of the Fe(II) complexes of siderophore complexes where the redox potentials have been measured over a range of pH values (59). This also explains the variation in reversibility of reduction as the pH changes, as the stability of the ferro-siderophore complex is much lower than the ferric complex, and the increased lability of ligand exchange and increased binding site competition from H+ may result in dissociation of the complex before the iron center can be reoxidized. 

Rhizobactin (40) is the siderophore of Rhizobium meliloti 328). It contains one ot-hydroxycarboxylic acid and two ot-amino acid units as probable binding sites for Fe ". Acid hydrolysis yields inter alia L-malic acid. The stereochemistry of the other two chiral centers is not known. 

The second group of hydroxamate-based chelators consists of biomimetic ferrichrome analogs modified by introducing hydrophobic amino acids between the template and the hydroxamic acid binding sites 59, 60, 66, 68, 70, 199 and 200. Since they function to withhold iron from cells in contrast to their original function of iron delivery, they were named reversed siderophores (RSF) . ... 

Ligand 3.147 is part of the class of siderands (synthetic siderophores), and displays further useful properties such as stability towards oxidation of the catechol binding sites and hydrolysis resistance. This represents one of the few examples where man-made molecules are more effective than their natural precursors. 

FIGURE 7 Examples of Fe ligands. (A) The bacterial hexadentate siderophore enterobactin. (B) The planar porphyrin phytochelatin. M denotes the metal binding site. Reprinted with permission from Stumm W., and J. J. Morgan. 1996. Aquatic Chemistry Chemical Equilibria and Rates in Natural Waters. Copyright 1996 Wiley, New York. 

Two binding sites are commonly found catecholate, as in enterobactin, and hydroxamate, the motif in desferrioxamine B. The resulting complex is targeted by a membrane-bound receptor and captured by the organism. The complex is transported across the cell membrane where the iron is reduced to iron(II), which has a lower affinity for the siderophore, and subsequently decomplexed. 

The effective molarity measured for [Phen2]PAAcPEI may be compared with that for enterobactin, the strongest microbial siderophore, containing three catechol units connected by a spacer. The effective molarity of a catechol unit towards a Fe(m) ion bound to another catechol unit contained in enterobactin is estimated to be 3 x 104 m [37]. Enterobactin contains three catechol units, whereas the Cu(ii) binding site of [Phen2]-paAcPEI consists of only two phenanthrolines. Nevertheless, the effective molarity observed for [Phen2]PAAcPEI is extraordinary for a synthetic system. 

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