Theoretical insights into the mechanism of redox switch in heat shock protein Hsp33.

Heat shock protein 33 (Hsp33) is activated in the presence of H2O2 by a very interesting redox switch based on a tetra-coordinated zinc-cysteine complex present in the fully reduced and inactive protein form. The oxidation of this zinc center by H2O2 induces formation of two S-S bridges and the zinc release followed by the protein unfolding. We report here a theoretical study of the step-by-step sequence of the overall process starting with the oxidation of the first cysteine residue and ending with the zinc release.

Oxidation reactivity of zinc-cysteine clusters in metallothionein.

Evaluating the reactivity of the metal-thiolate clusters in metallothionein (MT) is a key step in understanding the biological functions of this protein. The effects of the metal clustering and protein environment on the thiolate reactivity with hydrogen peroxide (H(2)O(2)) were investigated by performing quantum theory calculations with chemical accuracy at two levels of complexity. At the first level, the reactivity with H(2)O(2) of a model system ([(Zn)(3)(MeS)(9)](3-), MeS is methanethiolate) of the β domain cluster of MT was evaluated using density functional theory (DFT) with the mPW1PW91 functional.

Oxidation of zinc-thiolate complexes of biological interest by hydrogen peroxide: a theoretical study.

Zinc-thiolate complexes play a major structural and functional role in the living cell. Their stability is directly related to the thiolate reactivity toward reactive oxygen species naturally present in the cell. Oxidation of some zinc-thiolate complexes has a functional role, as is the case of zinc finger redox switches.