Zinc-containing metallothioneins

Lane, B., Kajioka, R. Kennedy, T. (1987). The wheat-germ Ec protein is a zinc-containing metallothionein. Biochemistry and Cell Biology 65, 1001-5. 

If zinc-containing domains lose their Zn2 they do not bind tightly to DNA. Regulation of the flow of zinc ions from storage sites in metallothioneins (Box 6-E) into transcription factors as well as into more than 300 enzymes poses interesting mechanistic questions.401... 

The metallothioneins have been found in several vertebrate species and in marine invertebrates.1452 Prinz and Weser purified a copper-containing metallothionein from Saccharomyces cerevisiae.1453 Another copper-binding protein was isolated from Neurospora crassa.1452 The first unequivocal demonstration of a metallothionein in a vascular plant was recently reported.1455 The amount of metallothionein in different species and tissues is variable. The concentration has been reported to increase up to 40-fold by the induction of its biosynthesis by certain metals such as cadmium or zinc. In new-born rat liver (one to four days old) the concentration of Zn- and Cu-metallothionein is 20 times that in 70-day-old adult rats.1456 There are several recent reports and reviews in this active area.1243,1467a k... 

K2. Kagi, J. H. R., and Vallee, B. L., Metallothionein A cadmium- and zinc-containing protein from equine renal cortex. J. Biol. Chem. 235, 3460-3465 (1980). 

Metallothioneins (MT) are unique 7-kDa proteins containing 20 cysteine molecules bounded to seven zinc atoms, which form two clusters with bridging or terminal cysteine thiolates. A main function of MT is to serve as a source for the distribution of zinc in cells, and this function is connected with the MT redox activity, which is responsible for the regulation of binding and release of zinc. It has been shown that the release of zinc is stimulated by MT oxidation in the reaction with glutathione disulfide or other biological disulfides [334]. MT redox properties led to a suggestion that MT may possesses antioxidant activity. The mechanism of MT antioxidant activity is of a special interest in connection with the possible antioxidant effects of zinc. (Zinc can be substituted in MT by some other metals such as copper or cadmium, but Ca MT and Cu MT exhibit manly prooxidant activity.)... 

In mammals, cadmium inhibits copper absorption across the intestinal mucosa (Aaseth and Norseth 1986). Intercorrelations of copper with cadmium and zinc in livers of polar bears (Ursus maritimus) are probably mediated by metallothioneins, which may contain all three metals (Braune etal. 1991). In rats, copper protects against nephrotoxicity induced by cadmium, provided that copper is administered 24 h prior to cadmium insult. Specifically, rats given 12.5 mg Cu/kg BW by way of subcutaneous injection 24 h before receiving 0.4 mg Cd/kg BW — when compared to a group receiving Cd alone — did not have excessive calcium in urine and renal cortex or excessive protein in urine. Thus, 2.8 mg Cu/kg BW protects against 0.25 mg Cd/kg BW (Liu et al. 1992). 

One example of the use of semiempirical methodology is provided in an article detailing a molecular-dynamics simulation of the beta domain of metallothionein with a semiempirical treatment of the metal core.73 The beta domain of rat liver metallothionein-2 contains three-metal centers. In this study, three molecular variants with different metal contents—(1) three cadmium ions, (2) three zinc ions, and (3) one cadmium ion and two zinc ions—were investigated using a conventional molecular dynamics simulation, as well as a simulation with a semiempirical quantum chemical description (MNDO and MNDO/d) of the metal core embedded in a classical environment. For the purely classical simulations, the standard GROMOS96 force-field parameters were used, and parameters were estimated for cadmium. The results of both kinds of simulations were compared to each other... 

Since zinc ions have no color their presence has often been overlooked. Zinc ions will doubtless be found in many more places within cells. Zinc is usually the major component of the bound metals in the metallothioneins (Box 6-E). These small 6.6-kDa proteins which contain 33% cysteine and bind as many as six ions of Cd2+, Hg2+, Cu2+, or Zn2+ per molecule are present in all animal tissues as well as in plants and some bacteria.)... 

Foetal and neonatal livers contain exceptionally high levels of copper compared to the adult organ. Thus, the livers of new-born rats contain as much as 20 times the level of copper and zinc metallothionein as that found in 70-day-old rats.1150 Again, a metallothionein from foetal bovine liver contained eight copper and two zinc atoms per molecule of protein.1151 These proteins can only be isolated with difficulty under oxygen-free conditions. It appears then that large amounts of copper (and zinc) are stored in the liver bound to metallothionein, and are mobilized as required for enzyme synthesis after birth. 

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