Zinc is present in almost 3,000 human proteins, and thus is essential for nearly all cellular functions. Zn is also a key constituent of enzymes involved in cell regulation. Consistent with its ubiquitous presence, total cellular Zn concentrations are typically very high (~200 μM), while the concentrations of free Zn ions in the cytoplasms of cells can be as low as a few hundred picomolar, maintained within a narrow range to avoid deficiency and toxicity. One feature of Zn that makes it so critical in cellular biology is its flexibility in coordination to different numbers and types of ligands. Zn can coordinate with anywhere between three and six N-, O- and S-containing ligands (such as histidine, glutamic acid, aspartic acid and cysteine), resulting in a large number of possible coordination chemistries. Zn tends to bind to metal sites of proteins with relatively high affinities compared to other metal ions which, aside from its important functions in enzymatic reactions, partly explains its ubiquitous presence in cellular enzymes.