Complexation of the Zn, Co, Cd, and Pb ions by metallothioneins: A QM/MM simulation

Complexation of divalent metal ions (Zn, Co, Cd and Pb) with metallothioneins (MT), typical low molecular proteins of diverse higher, organisms, has been theoretically studied within the all-electron approximation B3LYP/DZP. The active site of MT (metal ions and cysteine residues) adopts the structure, in which cadmium, cobalt and zinc ions reveal a tetrahedral location of the sulfur atoms. A pyramidal structure is typical for the coordination environment of the lead complexes in the MT active site. The Gibbs energies of the active site formation were calculated accounting the influence of water medium in terms of the IEFPCM approximation. For all studied metallothioneins, the metal-active site complexes demonstrate close Gibbs formation energies per one metal ion. The influence of the amino acid environment of the MT active sites has been studied with the two-shell ONIOM model and B3LYP/DZP:UFF approximation. A simple scheme for calculation of relative metal-MT binding energies has been developed. Even under the pronounced destabilization of the lead complexes by a polypeptide shell, the total energetic effect is sufficient to make accumulation of lead ions by metallothioneins more efficient than Cd and, especially, Zn and Co. The following general trend of stability of the MT complexes has been found: Co approximate to Zn << Cd << Pb. These results compared with the experimental regularities of bioaccumulation of heavy metal salts by bacteria Bacillus are briefly discussed. (C) 2017 Elsevier B.V. All rights reserved.