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Metal-dependent enzymes are a broad class of enzymes that require one or more metal ions for their biological activity. These metal ions can serve various roles, including direct participation in catalysis, stabilization of enzyme structure, and regulation of enzymatic activity. Approximately one-third to half of all known enzymes are classified as metalloenzymes. They catalyze a wide range of biochemical reactions essential for life. The metal ion(s) may act as electron donors or acceptors (redox roles), Lewis acids (to stabilize negative charges), or structural regulators that maintain the active conformation of the protein. Some metals participate directly in the catalytic mechanism; others influence enzyme function indirectly by stabilizing specific conformations or maintaining structural integrity. Common metals found in these enzymes include iron, copper, zinc, manganese, magnesium, nickel, molybdenum, and cobalt. Cells tightly regulate intracellular concentrations of free metals due to their potential toxicity while ensuring sufficient supply for metalloenzyme maturation and function. Specific biosynthetic pathways exist for assembling complex metalloprotein active sites and inserting correct metals into apoenzymes. Metalloenzymes are crucial targets in drug discovery because their unique dependence on specific metals offers opportunities for selective inhibition, and many pathogens rely on particular metalloenzymes absent from humans.
Inhibition of enzymatic activity via metal chelation or active site targeting
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