Structure—Reactivity Relationships of Metallothionein, a Unique Metal-Binding Protein

Abstract

Metallothionein is an intensively studied protein, which binds a variety of essential, toxic, and pharmacologically active metals, including Zn, Cd, Au, and Pt. Until recently, attention focused primarily on its biological properties and static features of its chemistry. It is now apparent that metallothionein is a remarkably reactive protein in metal exchange and ligand substitution reactions and in its interactions with a number of electrophilic compounds, which are both metallic and organic in nature. This unique behavior finds its basis in the dynamic character of its metal—ligand structure, which is sensitively probed by ¹¹³Cd NMR techniques. In an effort to relate the chemistry of metallothionein to its cellular activities, it is shown that the kinetic reactivity of the metal binding sites of metallothionein distinguishes it from other typical metalloproteins involved in enzyme catalysis. The rich inorganic chemistry of this structure is clearly important for some of its known functions and is suggestive of other novel roles for this protein in cells.