Metallothionein structure and reactivity

Abstract

The structure and chemistry of mammalian MTs with divalent (ZnII, CdII) and monovalent (CuI) metal ions pertinent to their role in biological systems are discussed. In human four MT isoforms designated MT-1 through MT-4 are found. The characteristic feature of these cysteine- and metal-rich proteins is the presence of two metal-thiolate clusters located in independent protein domains. The structure of these clusters is highly dynamic allowing a fast metal exchange and metal transfer to modulate activity and function of zinc-binding proteins.
Despite the fact that the protein thiolates are involved in metal binding, they show a high reactivity toward electrophiles and free radicals leading to cysteine oxidation and/or modification, and metal release. The unusual structural properties of MT-3 are responsible for
its neuronal growth inhibitory activity, involvement in trafficking of zinc vesicles in the CNS, and the protection against copper-mediated toxicity in Alzheimer's disease. MT-1/-2 also play a role in cellular resistance against a number of metal-based drugs.