Effect of cysteine vs. histidine on the electronic structure of Zn ²⁺ upon complex formation

The local electronic structure at Zn²⁺ ions during complex formation with histidine and cysteine has been studied by near edge x-ray absorption fine structure spectroscopy at the Zn L-edge. At pH ≅ 5 both histidine and cysteine have carboxylate and amino groups able to form complexes with cations in solution such as Zn²⁺. Compared to histidine, cysteine has an extra thiolate group which can chelate Zn²⁺. This investigation shows that histidine is chelating the Zn²⁺ ion mainly via the amino group, while cysteine chelates primarily via the thiolate group. The nature of the empty molecular orbitals involved in the transitions has been analyzed using density functional theory including the solvent effects. By comparing the calculated results with the experimental observations, we conclude that histidine affects primarily the Zn²⁺ electronic states of d-symmetry, while cysteine affects both s- and d-states. This mechanism is important for understanding the zinc sulfhydryl bond in zinc finger proteins, where cysteine and histidine in the protein are chelating Zn²⁺.