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

作者：Glusic Martina; Stare Jernej; Grdadolnik Joze; Vianello Robert^*

来源：Journal of Inorganic Biochemistry, 2013, 119: 90-94.

DOI：10.1016/j.jinorgbio.2012.11.004

• Cadmium detoxification
• Computational chemistry
• Density functional theory
• Metal ion affinity
• Solvent effects

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 pK(a)(SH) value by around 18 pK(a) 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.

• 出版日期2013-2