Zinc-binding protein (ZBP)

Zinc-binding proteins constitute a massive and diverse superfamily of proteins that utilize zinc ions for structural stability, catalytic activity, or regulatory control. It is estimated that nearly 10% of the human genome encodes proteins that bind zinc, encompassing a wide range of functional classes including enzymes, transcription factors, and storage proteins (Andreini et al., 2006, J. Proteome Res.). These proteins are essential for fundamental biological processes such as DNA synthesis, RNA transcription, and cellular metabolism (McCall et al., 2000, J. Nutr.). In clinical contexts, zinc-binding proteins like matrix metalloproteinases (MMPs) and histone deacetylases (HDACs) are frequently implicated in the progression of cancer and inflammatory disorders (Maret, 2013, Mol. Med.). Pharmacological intervention often involves the use of chelating agents or competitive inhibitors that interact directly with the zinc cation to modulate protein function. However, the ubiquity of zinc-binding motifs across the proteome presents a significant hurdle for drug development, as achieving high specificity for a single target without affecting other vital zinc-dependent processes remains difficult (Kambe et al., 2015, Physiol. Rev.). Zinc-binding proteins also play a role in neurobiology, where dysregulation of zinc homeostasis is linked to Alzheimer's and Parkinson's diseases (Watt et al., 2010, Chem. Soc. Rev.).

Other names

Zinc metalloproteinZinc finger proteinZn-binding protein

Drugs targeting zinc-binding proteins primarily function by coordinating with the zinc ion in the active site, often via a zinc-binding group (ZBG) like a hydroxamate or carboxylic acid, to inhibit enzymatic activity (McCall et al., 2000, J. Nutr.). Alternatively, some drugs disrupt the structural integrity of zinc finger domains to inhibit DNA binding and gene transcription (Maret, 2013, Mol. Med.).