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The detailed structural studies of lead that provide critical insights into the mechanism by which lead alters the activity of the proteins containing thoi-rich structural zinc-binding sites is reported. Lead binds in a three-coordinate mode and in a geometry that is fundamentally different from the natural coordination of zinc in these sites, which explains why lead disrupts the structure of zinc-binding peptides and thus provides the first detailed molecular understanding of the development toxicity of lead.

Metal-binding studies with DNA-binding domain of human estrogen receptor alpha and rat glucocorticoid receptor indicate that cobalt binds to both sites with similar affinities, while zinc binds to each of the two sites in the DNA-binding domains of steroid receptor. Data suggest there is hardly any interaction between the two metal sites in tems of metal binding.