Physiological zinc-binding proteins

Physiological zinc-binding proteins represent a vast and diverse group of proteins that require zinc ions for their structural integrity, catalytic activity, or regulatory functions (Vallee & Falchuk, 1993). Comprising approximately 10% of the human proteome, these proteins include enzymes like carbonic anhydrases and matrix metalloproteinases, as well as thousands of zinc-finger transcription factors (Andreini et al., 2006). Zinc serves as a crucial Lewis acid in enzymatic catalysis and stabilizes the tertiary structure of protein domains involved in DNA binding and protein-protein interactions (Maret, 2013). Dysregulation of zinc homeostasis or mutations in specific zinc-binding proteins are linked to numerous pathologies, including growth failure, immunodeficiency, and neurodegenerative disorders like Alzheimer's disease (Watt et al., 2010). While the entire class is not a single drug target, many individual members are major therapeutic targets, and pharmacological interventions often involve modulating zinc availability or specifically inhibiting zinc-dependent active sites (Overbeck et al., 2008).

Other names

Zinc-binding proteomeZinc-dependent proteinsZinc-metalloproteins

Drugs typically target these proteins by coordinating with the zinc ion in the active site to inhibit enzymatic activity (e.g., HDAC or ACE inhibitors), by chelating zinc to reduce its bioavailability, or by providing zinc as a nutritional cofactor to restore protein function (Maret, 2013; Overbeck et al., 2008).