Siderophores iron complexes

The uptake of siderophore-iron complexes by Gram-negative bacteria is energy dependent and occurs via specific outer membrane proteins. In the periplasmic space, it binds to its cognate periplasmic binding protein and is then actively transported across the cytoplasmic membrane by an ATP-trans-porter protein. Three principal mechanisms for transport through the outer membrane have been described ... 

When deficient in iron, bacteria and fungi produce and excrete to the extracellular medium low molecular weight, specific iron-carrier molecules, called siderophores. These siderophores bind ferric ions, to form soluble complexes. The complexed ferric ions are transported into the cell through high-affinity and energy-dependent receptor proteins located on the outer membrane. In Gram-negative bacteria, such as E. coli, the most studied system, siderophore-iron complexes are transported initially to the periplasm. 

Once the siderophore-iron complexes are inside the bacteria, the iron is released and utilized for vital cell functions. The iron-free hydroxamate siderophores are commonly re-excreted to bring in an additional iron load (Enterobactin is at least partially degraded by a cytoplasmic esterase This cycle is repeated until specific intracellular ferric uptake regulation proteins (Fur proteins) bind iron, and signal that the intracellular iron level is satisfactory, at -which point ne-w siderophore and siderophore-receptor biosynthesis are halted and the iron-uptake process stops. This intricate feedback mechanism allows a meticulous control over iron(III) uptake and accumulation against an unfavorable concentration gradient so as to maintain the intracellular iron(III) level within the required narrow window. Several excellent reviews concerning siderophore-iron transport mechanisms have been recently published i.3,i6, is,40,45,60-62 ... 

Figure 2 Siderophore-mediated iron-uptake systems in E. coli. Siderophore-iron complexes bind to transporter proteins located in the outer membrane (also known as OM), a barrier that is characteristic of Gram-negative bacteria. The region between the outer and inner is known as the periplasmic space. Specific carrier proteins such as FhuD transport iron fi om the outer membrane to the inner or cytosolic membrane (also known as CM). The TonB/ExbB/ExbD complex spans the inner and outer membranes and interacts with FepA, as shown, as well as all of the outer membrane receptors. The linkage that the TonB/ExbB/ExbD complex provides between the inner or cytosolic membrane to the outer membrane is thought to allow transmission of sufficient energy from the cytosol to drive siderophore-iron uptake across the outer membrane...

Most hexadenlate hydroxamate and catecholate siderophores are stereochernically restricted to the cis isomers. The stereochemistry of a range of siderophore iron complexes was determined by x-ray and CD methods (Table These isomers are stable in aqueous... 

Siderophores are iron-complexing compounds of low molecular weight that are synthesized by bacteria and fungi, and serve to deliver iron to the microbes. Because of their exclusive affinity and specificity for Fe3+, natural siderophores and synthetic derivatives have been exploited in the treatment of human iron-overload diseases. The most successfully used example is Desferal , which is the methane sulfonate derivative of iron-free ferrioxamine B, a linear trihydroxamate (Figure 3.2). Ferrioxamine was isolated in 1958 from the culture supernatant of Streptomyces... 

Thermodynamic Stability Constants for Iron(III)-Hexadentate Siderophore Mimic Complexes, Measured at 25°C... 

Fig. 14. Schematic representations of linear tetradentate side-rophore (H2L) complexes with different siderophore/iron stoichiometries. Coordinated water not shown for clarity.

Table 3 lists stability constants for complex formation from Fe + and a range of common ligands, all values being from one investigation. Further information on stabilities of iron complexes may be found in several later sections, especially Sections 5.4.5.5 and 5.4.5.6 on hydroxypyri-dinones and siderophores. 

A multiple-path mechanism has been elaborated for dissociation of the mono- and binuclear tris(hydroxamato)-iron(III) complexes with dihydroxamate ligands in aqueous solution. " Iron removal by edta from mono-, bi-, and trinuclear complexes with model desferrioxamine-related siderophores containing one, two, or three tris-hydroxamate units generally follows first-order kinetics though biphasic kinetics were reported for iron removal from one of the binuclear complexes. The kinetic results were interpreted in terms of discrete intrastrand ferrioxamine-type structures for the di-iron and tri-iron complexes of (288). " Reactivities for dissociation, by dissociative activation mechanisms, of a selection of bidentate and hexadentate hydroxamates have been compared with those of oxinates and salicylates. ... 

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