Proteins inhibition/metal binding

One of the more sensitive indicators of cadmium exposure is the inhibition of non-thionein hepatic metal binding proteins inhibition was observed in juvenile bluegills (Lepomis macrochirus)... 

Low Fe/Proteln (Fe <10-12/Molecule). Ferritin protein coats have multiple (8-12) binding sites for a variety of metals. Including Fe(II), Fe(IIl), V(IV), Mn(II), Tb(III), Cd(II), Zn(II), and Cu(II) (e.g., 5,34-36, and reviewed In Ref. 37). At least some of the metals bind at the three-fold channels. The location of the nucleatlon sites Is presently unknown. However, If the three-fold channels are the nucleatlon sites for core formation, core growth could block the channels, thus Inhibiting further accretion INSIDE the protein coat and could lead to the addition of Fe OUTSIDE the protein coat. Such an effect would obviate the sequestering function of the protein. Three forms of Fe have been observed bound to ferritin protein coats (apoferrltln) mononuclear, dlnuclear, and multlnuclear clusters. 

The regulation of the activity of enzymes by the binding of effector molecules is a ubiquitous and general principle for the fine timing and control of metabolic activity. Effector molecules are often low molecular weight organic compounds. Proteins and metal ions can also exercise the function of effectors. The effector molecules bind specifically to the enzymes and the binding results in inhibition or stimulation of enzymatic activity. 

Ferritin has also been compared with iron-dextran by the EXAFS technique.1108 The apoferritin controls the deposition of the core. Reconstitution of ferritin under a range of conditions always gives the same structure, which is not the case in the absence.of apoferritin. There are metal-binding sites on the protein shell. There is evidence for the binding of iron to apoferritin, probably by carboxyl groups, but there is little detailed information on these sites.1098 On the other hand, other metal ions inhibit the formation of ferritin and may do this by binding at or close to the iron sites. Of most significance appear to be results on Tb3+, Zn2+ and V02+,... 

To Elucidate Protein Topology. Numerous examples have been presented in the literature in which two His residues have been created at two different locations and then metalbinding used to identify helix position, orientation, or other types of protein topology. For example, a transmembrane segment in the human dopamine transporter (hDAT) was probed with new metal-binding sites. A bis-histidine site was created with a residue at position 375 pins neighboring residues. Inhibition of the transporter with Zn(II) coordination was observed only with histidine residues located at position 375 and those located at residue 371, 377, 378, or 379. The... 

Several proteins that exist in food (e.g., lactoferrin, ferritin, transferritin, heme protein) possess strong binding sites for iron. Reducing agents (ascorbate, cysteine, superoxide anion) to low pH causes release of iron from proteins and accelerates lipid oxidation (34). Some amino acids and peptides found in muscle foods (e.g., carnosine) are capable of chelating metal ions and inhibit their prooxidant activity (35, 36). 

Like pesticides, heavy metals are traditionally tested by enzyme inhibition or modulation of catalytic activity. Several metalloproteins behave as chelators for specific metals with no known catalytic reactions. Such heavy metal binding sites exist in metallothioneins and in various protein elements of bacterial heavy metal mechanisms and have been exploited for specific detection through affinity events. Nevertheless and as previously mentioned, bacterial resistance mechanisms can also be linked to catalytic pathways. For instance, c5rtochromes c3 and hydrogenases from sulfate and sulfur reducing bacteria [284,285] are well suited for bioremediation purposes because they can reduce various metals such as U(V) and Cr(VI) [286,287]. Cytochrome c3 has been reported to catalyse Cr(VI) and U(VI) reduction in Desulfovibrio vulgaris [288,289], suggesting... 

In plants, two kinds of metal-binding peptides or proteins are synthesized. Plant metallothioneins are inducible cysteine-rich entities very like those found in animals. Differential expression (induction) of metallothionein genes can be due to both variation of external heavy metal concentrations and the influence of various environmental factors. The principle role of plant metallothioneins seems to be in homeostasis rather than in metal detoxification. Plants are also known to have so-called phytochelatins, which are non-protein thiols specifically induced upon exposure to heavy metals. A close positive relationship between the concentrations of cadmium and phytochelatins in the plant shoot material has been observed and linked to the degree of growth inhibition (Keltjens and Van Beu-sichem, 1998). These observations make the use of phytochelatins promising for the assessment of heavy metal effect on plants. 

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