METALLOTHIONEINS

Metallothioneins are a class of protein characterized by a high cysteine content (up to 30% of the amino acid residues), low molar mass (approx. 6000 for the mammalian protein), and lack of aromatic amino acid residues. Remarkable metal binding properties have been reported both in vivo and in vitro. Chemical and spectroscopic studies have shown that an unusually wide range of metals bind to metallothionein. The metallated protein has been well characterized from mammalian sources, yeast, fungus, and crustaceans. Key structural properties have been determined for protein isolated from mammals, yeasts, fungus and crustaceans. Cd-113 and H-1 NMR techniques have been used successfully to characterize the structures in a number of different proteins. Together with X-ray diffraction results, analyses of these NMR data have established that in mammalian Cd-7-MT and Zn-7-MT, the metals are tetrahedrally coordinated in two isolated domains with stoichiometries of M(4)S(11) and M(3)S(9). Overall, the most extensively studied proteins contain Cu(I). Ag(I), Co(II) and Hg(II). Optical spectroscopy, and in particular circular dichroism and luminescence have provided details of a complicated metal binding chemistry whether metals are added directly to the metal free, apometallothionein, or to the zinc containing protein. Three structural motifs have been identified from studies of Cd(II), Zn(II), Hg(II), Cu(I) and Ag(I) binding. For rabbit liver metallothionein, the peptide chain forms metal thiolate clusters with stoichiometries of M(7)-S-20, M(12)-S-20 and M(18)-S-20 depending on which metal binds. The synchrotron-based techniques of XANES and XAFS have provided a wealth of information on the metal-thiolate bond lengths and coordination geometry of the bound metal, that together with structural information from two-dimensional H-1 NMR data should allow three-dimensional structures of a range of metallothioneins to determined in the near future.