Zinc plays both structural and catalytic roles in metalloproteins.

Zinc is bound to the catalytic site of zinc-dependent hydrolases by three amino acid residues, commonly histidines and glutamic acid, and to the structural site of gene transcription regulators by cysteine and histidine. Site-directed mutagenesis of even one catalytic-site ligand destroys enzyme activity without changing physical properties of the protein, including immunoreactivity. However, nutritional studies demonstrating loss of transcriptional activity upon zinc deprivation have not been reported.