Cadmium -substituted zinc proteins

Cadmium-substituted zinc proteins may also be active (Table 2.4), although usually at higher pH. This observation is readily explained in terms of the pAT of a coordinated water, which is expected to be higher than that of analogous zinc complexes because the cadmium ion is larger and polarizes the Cd—OH2 bond less. 

Varying ratios of the ligands 7V-(2-thiophenyl)-2,5-dimethylpyrrole and V-methylimidazole were used to form tetrahedral zinc complexes with S4, S3N, and S2N2 coordination spheres. X-ray structural analyses and IR spectra were recorded for all compounds and the relevance to zinc finger proteins was discussed. The comparison to cobalt and cadmium structures showed only minor differences, supporting the theory that changes on substituting these metals into zinc proteins would be minor.538... 

It is now established that cadmium, besides zinc, is accumulated in some native cysteine-rich proteins (e.g., metallothioneins) and the binding mode and sites in the protein are studied and largely understood.57 Also, the detection and study of native Cd-enzymes and Cd-substituted Zn-enzymes is just beginning at the time of writing (for a short survey see ref. 58). 

Recent high-resolution crystal structures of the wild-type E. coli enzyme and its complex with phosphate have enhanced our initial understanding of the enzyme mechanism, which was based on earlier lower-resolution structures of the same forms plus the E-P form of the cadmium-substituted enzyme. In all cases, the zinc ions are separated by about 4.0 A, and there are no protein ligands bridging the two zincs. The magnesium ion is located 4.8 A from the less solvent-exposed zinc (Zn2), to which it is linked by a bridging bidentate aspartate carboxylate, and 7.1 A... 

Cadmium-113 nuclear magnetic resonance studies of the cadmium substituted bovine superoxide dismutase were carried out Only a very small chemical-shift difference between the 2 Cd(Il) protein (Cd(II) is bound to the zinc site and the copper site is unoccupied) and the 2 Cd(ll)—2 Cu(I) enzyme (analogous to the reduced form of the native protein) was found. This was interpreted in that the imidazolate bridge is protonated at the Cu site after reduction. 

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.)... 

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