One His, two His…the emerging roles of histidine in cellular nickel trafficking

Biological environments present a complex array of metal-binding ligands. Metal-binding proteins have been the overwhelming focus of study because of their important and well-defined biological roles. Consequently, the presence of functional low molecular weight (LMW) metal-ligand complexes has been overlooked in terms of their roles in metallobiochemistry, particularly within cells. Recent studies in microbial systems have illuminated the different roles of L-histidine in nickel uptake, gene expression, and metalloenzyme maturation. In this focused critical review, these roles are surveyed in the context of the coordination chemistry of Ni(II) ions and the amino acid histidine, and the physico-chemical properties of nickel complexes of histidine. These complexes are fundamentally important to cellular metal homeostasis and further work is needed to fully define their contributions.