Zinc-dependent enzymes and zinc-binding proteins

Zinc-dependent enzymes and zinc-binding proteins constitute a large and diverse group of proteins where zinc ions play essential catalytic, structural, or regulatory roles (Maret, 2013, Metallomics). Zinc serves as a cofactor for approximately 10% of the human proteome, including critical enzymes such as carbonic anhydrases, matrix metalloproteinases (MMPs), and histone deacetylases (HDACs) (Andreini et al., 2006, Journal of Proteome Research). These proteins are involved in a wide array of biological processes, ranging from DNA replication and gene expression to metabolism and signal transduction (Vallee & Falchuk, 1993, Physiological Reviews). In disease states, dysregulation of zinc-binding proteins is linked to cancer, cardiovascular disorders, and neurodegeneration (Watt et al., 2010, Frontiers in Bioscience). Therapeutic strategies often involve small-molecule inhibitors that bind to the zinc ion within the protein's active site, effectively blocking its function (Chen et al., 2019, Journal of Medicinal Chemistry). However, the ubiquity of zinc-binding motifs across various protein families presents a significant challenge for drug design, as achieving high specificity is necessary to minimize adverse effects (Parkin, 2004, Chemical Communications).

Other names

MetalloproteinsZinc-binding proteinsZinc-dependent enzymesZinc finger proteins

Drugs typically interact with these targets by chelating the zinc ion in the active site or by displacing the water molecule coordinated to the zinc, thereby inhibiting enzymatic activity or disrupting structural motifs like zinc fingers (Chen et al., 2019, Journal of Medicinal Chemistry).