Metallothioneins metal-binding site

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... 

R31. Elucidation of metallothionein structure by cadmium-113 NMR Otvos, J. D. Armitage, I. M. in Biochemical Structure Determination by NMR Bothner-By, A. A. Glickson, J. D. Sykes, B. D. Eds. Dekker New York, 1982 pp. 65-96, 43 references. Covers structural characterization of metal-binding sites of metallothioneins from crab hepatopancreas and rabbit liver. 

The objective in this section of this chapter is to illustrate how " Cd NMR methods were used to provide the first definitive evidence for the existence of polynuclear Cd clusters in MT, which was followed by the elucidation of the 3D solution structure of a variety of MTs and the establishment of the relative affinities of the multiple metal binding sites for Cd, Zn and Cu [132,136,138,143,154,219,220,225]. For a more in depth discussion on metallothioneins in general, the reader is referred to Chapter 11, Cadmium in Metallothionein by Freisinger and Vas in this volume. 

In response to the presence of detrimental Cd +, Hg +, Pb +, and other heavy metal ions, the human hver and kidneys synthesize more metallothionein, an unusual small protein in which approximately one-third of the 61 amino acid residues are cysteine see Metallothioneins). The frequency and juxtaposition of sulfhydryl groups provide strong binding sites for several heavy metal ions. Though not as profusely as metallothionein, many proteins contain sulfhydryl groups that may become metalated by toxic heavy metal ions such as Cd +, Hg +, and Pb +, and it is widely believed that this complex formation explains the toxicity of these metal ions. The exact proteins where the most consequential damage occurs remain uncertain. 

Binding those metal ions in a metalloprotein usually prevents them from entering into these types of reactions. For example, transferrin, the iron-transport enzyme in serum, is normally only 30 percent saturated with iron. Under conditions of increasing iron overload, the empty iron-binding sites on transferrin are observed to fill, and symptoms of iron poisoning are not observed in vivo until after transferrin has been totally saturated with iron. Ceruloplasmin and metallothionein may play a similar role in preventing copper toxicity. It is very likely that both iron and copper toxicity are largely due to catalysis of oxidation reactions by those metal ions. 

Zinc can play a structural role in proteins and it does this by binding sulfur and/or nitrogen (in cysteine or histidine residues, respectively) [90, 97]. For example, the zinc finger motif which is found in several structures of zinc-binding proteins, contains a motif of Cys and His side chains, four in all, that bind the zinc ion. This motif is also used to bind certain other metal ions such as iron (in rubredoxin), copper (in plastocyanin and azurin), and cadmium (in metallothionein) and so is not entirely specific to zinc. On the other hand, it is an entirely different binding site from that preferred by magnesium ions. 

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