Regulation of zinc-dependent enzymes by metal carrier proteins

Zn²⁺ ions are essential in many physiological processes, including enzyme catalysis, protein structural stabilization, and the regulation of many proteins. The affinities of proteins for Zn²⁺ ions span several orders of magnitude, with catalytic Zn²⁺ ions generally held more tightly than structural or regulatory ones. Metal carrier proteins, most of which are not specific for Zn²⁺, bind these ions with a broad range of affinities that overlap those of catalytic, structural, and regulatory Zn²⁺ ions and are thought to be responsible for distributing the metal through most cells, tissues, and fluid compartments. While little is known about how many proteins obtain or release these ions, there is now considerable experimental evidence suggesting that metal carrier proteins may be responsible for transferring metals to and from some Zn²⁺-dependent proteins, thus serving as a major regulatory factor for them. In this review, the biological roles of Zn²⁺ and structures of Zn²⁺ binding sites are examined, and experimental evidence demonstrating the direct participation of metal carrier proteins in enzyme regulation is discussed. Mechanisms of metal ion transfer are also offered, and the potential physiological significance of this phenomenon is explored.