metalloprotein

Metalloproteins are proteins that contain one or more metal ions as a tightly bound cofactor essential for their structure or activity. The metal may be part of a prosthetic group, such as heme, or coordinated directly in the protein’s active site or structural core. Metals enable catalysis, substrate binding, or stabilization of charged intermediates, and in some cases play a structural role in maintaining protein conformation.

Metals are bound by specific ligands within the protein, often including histidine, cysteine, or aspartate side chains, sometimes in combination with nonprotein ligands. The presence and identity of the metal influence the protein’s redox chemistry, Lewis acidity, and catalytic mechanism. Some metalloproteins participate in redox reactions, whereas others provide structural support or chaperone functions.

Common metal ions found in metalloproteins include iron, copper, zinc, manganese, nickel, cobalt, molybdenum, and tungsten. Iron and copper frequently participate in electron transfer and redox reactions; zinc often serves catalytic or structural roles without undergoing redox cycling. Manganese, nickel, and molybdenum are key in various enzymatic activities, such as oxidoreductases, and in nitrogen and sulfur metabolism.

Examples include hemoglobin and myoglobin (iron in a heme group for oxygen binding), cytochromes (iron-containing electron carriers), carbonic anhydrase and alkaline phosphatase (zinc-dependent enzymes), copper-containing enzymes like ceruloplasmin and cytochrome c oxidase, and metalloproteases such as matrix metalloproteinases. SOD enzymes may use copper and zinc or manganese.

Metalloproteins are essential for processes including oxygen transport, respiration, digestion, detoxification, and metabolism; disruption of metal homeostasis can lead to disease.