Metal ion-binding sites in proteins

Damall, D.W and Birnbaum, E.R. (1970) Rare earth metal ions as probes of calcium ion binding sites in proteins neodunium(III) acceleration of the activation of trypsinogen. Journal of Biological Chemistry, 245 (23), 6484-6486. 

Even though the applicability of the halide ion relaxation technique to studies of non-metal anion binding sites in proteins was demonstrated at an early stage, most interest has until recently been devoted to studies of halide ion coordination to protein-bound metal ions. Some studies of metal-free proteins have been described above... 

An alternative approach is that adopted by Horrocks and co-workers, where the aromatic residues in metal-binding proteins are used as sensitizers. Since the distance between the metal and the donor is effectively fixed, this provides a rigid scaffold for the experiment, and the absence of a directly conjugated pathway between the metals means that Forster (through space) energy transfer can be assumed. The r-6 distance-dependence of this means that the extent of sensitized emission from the lanthanide ion provides information on the spatial relationship between the metal-ion binding site (lanthanide ions often bind at Ca2+ sites) and nearby aromatic residues. 58-60... 

Voss, J., Hubbell, W. L., and Kaback, H. R. (1995) Distance determination in proteins using designed metal ion binding sites and site-directed spin labeling application to the lactose permease of Escherichia coli. Proc. Natl. Acad. Sci. USA 92, 12300-12303. 

Unlike the other alkaline earth and transition metal ions, essentially on account of its small ionic radius and consequent high electron density, Mg2+ tends to bind the smaller water molecules rather than bulkier ligands in the inner coordination sphere. Many Mg2+-binding sites in proteins have only 3, 4 or even less direct binding contacts to the protein, leaving several sites in the inner coordination sphere occupied by water, or in the phosphoryl transferases, by nucleoside di- or triphosphates. 

In addition to enthalpic contributions, the entropy effects accompanying protein-metal ion interactions are substantial. These effects manifest themselves in the desolvation of the metal ion and its binding site. However, as the metal ion binds to a protein, the entropy gain of solvent release may be offset to some degree by the reduction of the conformational entropy of the polypeptide chain as it becomes more firmly bound... 

For the most part, adequate copper is received in diet and widespread human deficiencies do not occur, but deficiencies may arise because of antagonists. The metals Cd, Hg, Ag and Zn interfere with copper metabolism, probably by competing for copper-binding sites in proteins. Ascorbic acid depresses intestinal absorption of copper56 (in contrast to iron). Some proteins in the diet adversely affect utilization of copper. The sulfide ion is a well known inhibitor of copper absorption, since it forms copper(II) sulfide which is insoluble.56... 

AU the transferrins crystalhzed to date share a couunon structure, an example of which is shown in Figure 3. The protein has two structurally homologous lobes of roughly 330 residues each, with a high sequence identity between them. Each lobe comprises two domains with a central mixed p-sheet surrounded by o -hehces. Between the domains is a cleft in which the metal ion binding site contained in each lobe is situated. One ferric ion binds to each site, with a carbonate ion binding concomitantly with each metal. 

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