Zinc Finger-Dependent Gene Expression by pZn

Modulation of Zinc Finger-Dependent Gene Expression by pZn 

Since thionein is usually found in the metal-saturated form Mcy-thionein, the search for its biological function has been focused in the past primarily on roles as a metal repository in cells and tissues exposed to elevated concentrations of Zn , Cu , Cd , and others (Webb 1987), or as an in vitro donor of metals (Zn, Cu) to newly synthesized apoforms of metalloenzymes, such as carbonic anhydrase, alkaline phosphatase, and superoxide dismutase (Bremner 1991). However, as biosynthesis provides for a steady supply of the metal-free and metal-seeking apoprotein thionein, it is equally important to view the role of this form as a powerful intracellular acceptor and competitor for metal ions, among them in particular for zinc. In fact, it is chemically most reasonable to consider both Zny-thionein and thionein as conjugates of a zinc donor/zinc acceptor couple whose concentrations fix pZn and thereby regulate the availability of zinc within the cell. Values for the average apparent stability constant, pH 7.o determined by two independent methods for pH 7.0, are listed in Table 1. 

The binding isotherm calculated from this stability constant assuming cooperative cluster formation of Zny-thionein as a function of pZn is shown in Fig. 1. The curve, centered about logA n, pH 7.0 = 12.8, divides the continuum of affinities of zinc-binding systems into the weaker ones which are thermodynamically accessible to competition by thionein, on the left, and into the stronger ones to which Znv-thionein may donate the metal, on the right. 

HEPES calculated from the average apparent association constant for Zm in human Zn thionein, zn pH7.o = 7 x  

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