Iron-binding molecule

The effect of the amino acid spacer on iron(III) affinity was investigated using a series of enterobactin-mimic TRENCAM-based siderophores (82). While TRENCAM (17) has structural similarities to enterobactin, in that it is a tripodal tris-catechol iron-binding molecule, the addition of amino acid spacers to the TRENCAM frame (Fig. 10) increases the stability of the iron(III) complexes of the analogs in the order ofbAla (19)complex stability is attributed to the intramolecular interactions of the additional amino acid side chains that stabilize the iron-siderophore complex slightly. 

Because of the low solubility of Fe(II) and Fe(III) in a medium corresponding to the cytoplasm of living cells, it is extremely improbable that ionized iron exists in the cytosol. Thus, iron is present either in metabolically active cell components or bound to intracellular ligands, and specific iron-binding molecules have evolved to maintain iron in soluble form useable by the cell. 

In the vertebrate kingdom, where elaborate circulatory systems serve tissues with widely varying iron requirements, the transferrins, comprising a more complex and more subtle class of iron-binding molecules, have evolved for the transport of iron. Serum transferrin is the prototype... 

Uptake and distribution of gallium in organisms appears to be influenced by binding to at least three iron-binding molecules. 

Ferritin, an iron-binding protein, prevents ionized iron (Fe ) from reaching toxic levels within cells. Elemental iron stimulates ferritin synthesis by causing the release of a cytoplasmic protein that binds to a specific region in the 5 nontranslated region of ferritin mRNA. Disruption of this protein-mRNA interaction activates ferritin mRNA and results in its translation. This mechanism provides for rapid control of the synthesis of a protein that sequesters Fe +, a potentially toxic molecule. 

Finally, animal, plant and microbial tissues have been shown to contain the iron storage protein ferritin. The animal protein has been extensively studied, but the mechanism of iron binding has not been completely resolved (29). Animal tissues contain, in addition, a type of granule comprised of iron hydroxide, polysaccharide and protein. The latter, called hemosiderin, may represent a depository of excess iron (30). Interestingly, a protein with properties parallel to those of ferritin has been found in a mold. Here the function of the molecule can be examined with the powerful tools of biochemical genetics (31). 

This receptor-mediated endocytotic pathway has been especially well studied in the uptake of iron from blood plasma. Iron, because of its very low-solubility product (< 1(T17 at pH 7.4), is transported in plasma bound to the iron-binding protein transferrin. Two Fe3+ ions bind to each transferrin molecule. Entry into... 

Under normal physiological conditions, iron is transported in serum by transferrin, an 80 kDa bilobal protein with two almost identical iron-binding sites, one in each half of the molecule. 

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. 

Modular design. Synthetic molecules were constructed of multiple, closely related nonsymmetric repeat units that can be covalently attached from either end. This approach allows rational design of various congeners, controlling their physical properties, such as iron-binding capacities and partition coefficients (lipophilic/hydrophilic... 

Transferrin plays a major role in the transport and cellular uptake of thorium (Peter and Lehmann 1981). Thorium can be displaced from transferrin by an excess of iron, but it is not known whether thorium and iron bind to the same sites on the transferrin molecule. It has also been determined that thorotrast (Th02 colloid) blocks the uptake of labelled protein by the RES in female rabbits and in both male and female rats (Hyman and Paldino 1967). The mechanism of the blockade is not clear. Sex differences were found in rabbits but not in rats. The particle size of the Thorotrast colloid influences its effect on the uptake of protein only particles larger than 1 pm will interfere with uptake of protein by the RES. 

Murrell, J. N. The Potential Energy Surfaces of Polyatomic Molecules. Vol. 32, pp. 93—146. Neilands,J.B. Naturally Occurring Non-porphyrin Iron Compounds. Vol. 1, pp. 59—108. Neilands,J.B. Evolution of Biological Iron Binding Centers. Vol. 11, pp. 145—170. 

A solution of the iron-transport protein, transferrin (Figure 7-4), can be titrated with iron to measure the transferrin content. Transferrin without iron, called apotransferrin, is colorless. Each molecule, with a molecular mass of 81 000, binds two Fe3+ ions. When iron binds to the protein, a red color with an absorbance maximum at a wavelength of 465 nm develops The absorbance is proportional to the concentration of iron bound to the protein. Therefore, the absorbance may be used to follow the course of a titration of an unknown amount of apotransferrin with a standard solution of Fe3+. 

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