Metal binding metallothionein

There is concern over the toxicity of a nnmber of metals and metalloids, and their oxyanions. As for antibiotics, the genes for resistance are often plasmid-bome. There are several mechanisms that may operate—redaction, methylation, efflnx, and the synthesis of metal-binding metallothioneins. The following text illustrates aspects of these mechanisms. 

Otvos, J.D., Petering, D.H. and Shaw, C.F. Ill (1989) Structure - Reachvity Relationships of Metallothionein, a Unique Metal-Binding Protein. Comments on Inorganic Chemistry, 9,1-35. 

Teigen SW, Andersen RA, Daae HL, Skaare JU. 1999. Heavy metal content in liver and kidneys of grey seals Halichoerus grypus) in various life stages correlated with metallothionein levels some metal-binding characteristics of this protein. Environ Toxicol Chem 18 2364-2369. 

Metallothioneins are a group of non-enzymatic, low-molecular mass (6-7 kDa) metal-binding proteins. They play an important role in the detoxification of a number (Zn, Cu, Cd, and Hg) of trace metals (Chassaigne and Lobinski 1998). 

The detection of metal-binding proteins, especially of Cd- and Hg-binding metallothioneins or of the merR protein, induced numerous studies of model compounds of Cd and Hg with more or less simple sulfur- and selenium-containing ligands. 

In mammals, as in yeast, several different metallothionein isoforms are known, each with a particular tissue distribution (Vasak and Hasler, 2000). Their synthesis is regulated at the level of transcription not only by copper (as well as the other divalent metal ions cadmium, mercury and zinc) but also by hormones, notably steroid hormones, that affect cellular differentiation. Intracellular copper accumulates in metallothionein in copper overload diseases, such as Wilson s disease, forming two distinct molecular forms one with 12 Cu(I) equivalents bound, in which all 20 thiolate ligands of the protein participate in metal binding the other with eight Cu(I)/ metallothionein a molecules, with between 12-14 cysteines involved in Cu(I) coordination (Pountney et ah, 1994). Although the role of specific metallothionein isoforms in zinc homeostasis and apoptosis is established, its primary function in copper metabolism remains enigmatic (Vasak and Hasler, 2000). 

Chan, J. Huang, Z. Merrifield, M. E. Salgado, M. T. Stillman, M. J. Studies of metal binding reactions in metallothioneins by spectroscopic, molecular biology, and molecular modeling techniques. Coord. Chem. Rev. 2002,... 

Andersen, R.A., K.D.H. Eriksen, and T. Bakke. 1989. Evidence of presence of a low molecular weight, non-metallothionein-like metal-binding protein in the marine gastropod Nassarius reticulatus L. Comp. Bio-chem. Physiol. 94B 285-291. 

Webb, M. In Metallothionein II, Proceedings of the 2nd International Meeting on Metallothionein and Other Low Molecular Weight Metal-Binding Proteins, Kagi,... 

Kagi, J. H. R., Nordberg, M. (eds.) Metallothionein. Proc. First Internal. Meet. Metall-othionein and Other Low Molecular Weight Metal-binding Proteins. Zurich, July 17-22, 1978, Basel-Boston-Stuttgart, Birkhauser, 1979, p. 378... 

The binding of transcription factors to nucleotide sequences, which facilitates gene transcription, can be influenced by chemicals. For example, cadmium binds to a metal-binding protein factor, MFF-1, in place of zinc and so induces metallothionein synthesis. This, as it happens is a detoxication, as metallothionein binds cadmium. 

MEOS microsomal ethanol oxidizing system, mercapto- — SH group, metallothionein metal-binding protein, methylation addition of a methyl group. 

If animals ingest excessive amounts of Zn(n), Cd (II), Hg(II), or Cu(I) their livers and kidneys accumulate these metals as complexes of proteins called metallo-thioneins/1 e In mammals at least three related genes encode these metal-binding proteins. The best known, metallothionein II, has a highly conserved 61-residue sequence containing 20 cysteine residues and no aromatic residues. 

The two clusters differ in their metal-binding properties. Mammalian Cd, Zn metallothionein contains four Cd ions in cluster A and two Cd ions and one Zn ion in cluster B. 1157,1159 Calf liver metallothionein contains three Cu ions in cluster B with Cd-displaceable zinc ions in cluster A.1160 Studies on the binding of zinc and cadmium to human liver metallothionein show that binding occurs first in cooperative fashion to cluster A, followed by cooperative binding to cluster B. Incubation of the 7Cd metallothionein resulted in loss of Cd ions from cluster B initially.1161... 

Grill, E., Winnacker, E.-L. Zenk, M.H. (1987). Phytochelatins, a class of heavy metal binding peptides from plants are functionally analogous to metallothioneins. Proceedings of the National Academy of Sciences (USA) 84, 439-43. 

Winge, D.R., Nielson, K.B., Gray, W.R. Hamer, D.H. (1985). Yeast metallothionein sequence and metal-binding properties. Journal of Biological Chemistry 260, 14464-70. 

Metallothionein proteins are the most abundant intracellular, metal-binding proteins (Andrews, 2000). Four metallothionein isoforms have been identified in the mouse (MT-I-MT-IV) and are clustered within 50 kilobases of each other. In humans, there is one MTII gene and a cluster of MT I genes on chromosome 16 (Searl et al., 1984 West et al., 1990 Heuchel et al., 1995). The mammalian metallothioneins generally consist of 61 amino acids and 20 of these are cysteines (Heuchel et al., 1995). These cysteines are important for the binding of such bivalent metal ions, such as zinc, copper and cadmium. 

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