Metallothioneins primary structure

Metallothioneins from Neurospora crassa contain only 25 amino acid residues, but the primary structure is quite similar to the N-terminal part of the mammalian proteins.1454 These data indicate that the gene that codes for the Neurospora crassa metallothionein is evolutionary related to the gene of the vertebrate metallothioneins. Equine metallothionein exists in two major variants (metallothionein 1A and metallothionein 2A), which show remarkable similarities. Some allelic polymorphic variants also occur in man, horse and rabbit. Recent developments have been comprehensively reviewed.14678... 

Four isoforms of mammalian MT (from MT-1 to MT-4) have been found in addition more than 13 metallothionein-like proteins have been discovered in humans [14]. There are 11 genes (MT-IA, B, E, F, G, H, I, J, K, L, and X) for isoform MT-1 and one gene for each another isoform [15]. Differences between individual isoforms arise mainly from posttranslational modifieations, small changes in the primary structure. Affinity for various... 

Olafson RW, WD McCubbin, CM Kay (1988) Primary- and secondary-structural analysis of a unique prokaryotic metallothionein from a Synechococcus sp. cyanobacterium. Biochem J 251 691-699. 

As the focus of this review is on copper-dioxygen chemistry, we shall briefly summarize major aspects of the active site chemistry of those proteins involved in 02 processing. The active site structure and chemistry of hemocyanin (He, 02 carrier) and tyrosinase (Tyr, monooxygenase) will be emphasized, since the chemical studies described herein are most relevant to their function. The major classes of these proteins and their origins, primary functions, and leading references are provided in Table 1. Other classes of copper proteins not included here are blue electron carriers [13], copper-thiolate proteins (metallothioneines) [17], and NO reductases (e.g., nitrite [NIR] [18] or nitrous oxide [19]). 

Metallothioneins are a unique and widely distributed group of proteins. They are characterized by their low molecular weight (—6000), high cysteinyl content, and the ability to bind substantial numbers of metal ions (43). The proteins bind copper and zinc, thereby providing a mobile pool as part of the normal metabolism of these elements, and offer protection from the invasion of inorganic forms of the toxic elements cadmium, lead, and mercury. In addition, other metals, such as iron and cobalt, can be induced to bind. XAS is ideally suited to probe the environment of these different metal atoms (see Fig. 1), and the structural interpretations obtained from an analysis of the EXAFS data obtained in several such studies are summarized in Table 1(44). Thus, in each case, the data are consistent with the primary coordination of the metal deriving from the cysteinyl residues. 

Fig. 6.1 Model of the molecular structure of mammalian metallothionein, showing the primary sequence, and two topologically separate metal-thiolate clusters. (After Otvos and Armitage 1980.)...

Fig. 6.2 Three-dimensional structure of the metallic domains of the complex of CdyMT, and primary model of mammalian metallothionein.

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