engleski

Binding of cadmium dication to glutathione facilitates cysteine -SH deprotonation: A computational DFT study

Density functional theory calculations were employed to investigate the nature of binding between the physiological form of glutathione (GSH) and cadmium dication (Cd2+) in aqueous solution. The results revealed that, upon complexation, the cysteine -SH group gets deprotonated by the neighboring glycine carboxylate, reverting the latter to its unionized form, with not enough nucleophilicity to coordinate Cd2+. This proton transfer is facilitated by the formation of favorable Cd2+\S- coordination, which reduces cysteine pKa(SH) value by around 18 pKa units, and produces adduct in which GSH interacts with Cd2+ only through the cysteine thiolate anion and the ionized glutamine carboxylic group. Subsequent deprotonation of the glycine -COOH moiety to the bulk solvent yields a system 9.4 kcal mol-1 higher in energy, which makes this process unfeasible. We found our results to be fully consistent with vibrational and NMR spectroscopic measurements reported earlier.

cadmium detoxification; computational chemistry; density functional theory; metal ion affinity; sSolvent effects

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