The solution and complexation chemistry of zinc ions is the basis for biology. In living organisms, redox-inert has only one valence state: Zn(II). Its coordination environment in proteins limited by oxygen, nitrogen, sulfur donors from side chains a few amino acids. an estimated 10% all human proteins, catalytic or structural function remains bound during lifetime protein. However, other bind reversibly with dissociation association rates commensurate requirements regulation, transport,...

We postulate a novel and general mechanism in which the redox-active sulfur donor group of cyst(e)ine confers oxidoreductive characteristics on stable zinc sites proteins. Thus, present, an earlier, accompanying manuscripts [Maret, W., Larsen, K. S. & Vallee, B. L. (1997) Proc. Natl. Acad. Sci. USA 94, 2233–2237; Jiang, L.-J., Maret, W. (1998) 95, 3483–3488; Jacob, C., 3489–3494] demonstrate that interactive network featuring multiple zinc/sulfur bonds as found clusters metallothionein...

Metallothionein (MT), despite its high metal binding constant (KZn = 3.2 x 10(13) M-1 at pH 7.4), can transfer zinc to the apoforms of enzymes that have inherently lower stability constants. To gain insight into this paradox, we studied between and MT. Zinc be transferred in both directions-i.e., from thionein (the apoform MT) MT apoenzymes. Agents mediate or enhance been identified provide kinetic pathways either direction. does not all seven atoms an apoenzyme, but apparently contains...

Thionein (T) has not been isolated previously from biological material. However, it is generated transiently in situ by removal of zinc metallothionein under oxidoreductive conditions, particularly the presence selenium compounds. T very rapidly activates a group enzymes which bound at an inhibitory site. The reaction selective, as apparent fact that does remove catalytic sites metalloenzymes. instantaneously reverses inhibition with stoichiometry commensurate its known capacity to bind...

Mammalian metallothionein has been postulated to play a pivotal role in cellular zinc distribution. All seven of its metal atoms are bound with high thermodynamic stability two clusters buried deeply the molecule. If protein is function delivery, there must be biological mechanism facilitate release. One means achieve this would labilization by interaction an appropriate ligand. To search for such mediator, we have designed rapid radiochromatographic method that can detect changes content...

The release and transfer of zinc from metallothionein (MT) to zinc-depleted sorbitol dehydrogenase (EC 1.1.1.14 ) in vitro has been used explore the role MT cellular distribution. A 1:1 molar ratio is required for full reactivation, indicating that only one seven atoms transferred this process. Reduced glutathione (GSH) disulfide (GSSG) are critical modulators both rate ultimate number transferred. GSSG increases 3-fold, its concentration major determinant efficient transfer. GSH a dual...

Each of the seven Zn(II) ions in Zn3S9 and Zn4S11 clusters human metallothionein is a tetrathiolate coordination environment. Yet analysis association with thionein, apoprotein, dissociation from using fluorescent chelating agents FluoZin-3 RhodZin-3 reveal at least three classes sites affinities that differ by 4 orders magnitude. Four are bound an apparent average log K 11.8, methods employed, their binding indistinguishable. This property makes thionein strong agent. One ion relatively...

Metallothionein (MT) localizes in the intermembrane space of liver mitochondria as well cytosol and nucleus. Incubation intact with physiological, micromolar concentrations MT leads to import into where it inhibits respiration. This activity is caused by N-terminal β-domain MT; this system, isolated C-terminal α-domain inactive. Free zinc respiration at commensurate content either or β-domain, indicating that inhibition involves delivery mitochondria. Respiratory uncoupled identifies...