Zinc-dependent protein

Zinc-dependent proteins represent a broad category of molecules that require zinc ions for catalytic activity, structural integrity, or regulatory functions. In humans, this class includes vital enzymes such as matrix metalloproteinases (MMPs), which manage extracellular matrix remodeling, and histone deacetylases (HDACs), which are central to epigenetic regulation (West and Johnstone, 2014). In the context of bacterial pathogens, zinc-dependent proteins like metallo-beta-lactamases (MBLs) provide resistance against carbapenem antibiotics, posing a significant threat to global health (Bahr et al., 2021). Other bacterial zinc-dependent proteins include collagenases and tetanus toxins, which are critical for virulence and host tissue degradation. Therapeutic intervention typically involves small molecules that coordinate with the zinc ion to block the active site or chelating agents that strip the metal from the protein. However, because zinc is a cofactor for nearly 10% of the human proteome, achieving selectivity is a major challenge to avoid interfering with essential processes like DNA binding by zinc-finger transcription factors (Andreini et al., 2006). Consequently, drug development in this space focuses on high-affinity ligands that can distinguish between the specific coordination geometries of different zinc-binding sites.

Other names

Zinc metalloproteinZinc-binding proteinZinc-dependent enzymeMetalloprotein

Inhibition of catalytic activity through zinc chelation or competitive binding at the zinc-coordinated active site.