Function and Coordination Chemistry of Cd II in Metalloregulatory Proteins

1 General Overview of Metalloregulatory Proteins for Heavy Metals 

With metal ions found in approximately a third of all biomolecules [2] there has been significant interest in understanding the mechanisms and coordination chemistry, associated with the transport and regulation of these metal ions. In addition to the essential roles these metal ions play, an excess as a result of misregulation, frequently is associated with various disease states. Furthermore, some metal ions and particularly heavy metal ions, can be exclusively associated with toxicity. Nature has therefore evolved metalloregulatory proteins for heavy metal ion detoxification, which due to the soft nature of the heavy metal irais, is often dominated by Cys coordination chemistry. 

SmtB and ArsR have evolved from a common evolutionary origin. They function as a repressor binding to, in the case of SmtB, the smt operator-promoter in the absence of metal ions. On binding Zn(II), the SmtB repressor changes conformation, dissociates from the DNA and induces expression of a metallothionein, a class of cysteine-rich low-molecular-weight proteins. 

The first metallothionein to be isolated was in 1957 from horse kidney tissue and found to contain Cd(II) [3]. They are believed to play a role in metal ion regulation and detoxification, and display fascinating coordination chemistry with a range of 

Cd(Il)-substituted proteins, in which the native metal ion has been replaced with the spectroscopically richer Cd(ll), are discussed in detail in Chapter 6. in the following two sectiOTis of this chapter, the Cd(ll) coordination chemistry of two Cd(n) metalloregulatoiy proteins, CadC and CmtR, are described. 

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