metalloproteins

Metalloproteins are proteins that contain a metal ion as an integral part of their structure or catalytic mechanism. The metal is typically bound at a defined site, often coordinated by amino acid ligands or by prosthetic groups such as heme or iron-sulfur clusters. Metals may be tightly bound or bound transiently during turnover.

Common metals include iron, zinc, copper, manganese, nickel, cobalt, and magnesium. Metalloproteins encompass heme proteins (iron porphyrin) such as hemoglobin and cytochromes; non-heme iron proteins including iron-sulfur cluster proteins (ferredoxins) and non-heme iron enzymes; zinc metalloenzymes (carbonic anhydrase, alkaline phosphatase); and copper proteins (cytochrome c oxidase, plastocyanin). Nickel- and cobalt-containing enzymes (urease, hydrogenase; methylmalonyl-CoA mutase and various B12-dependent enzymes) also play key roles.

Functions: Metals enable electron transfer, catalysis, and substrate activation. They can act as redox centers (iron, copper, manganese), stabilize transition states, or polarize substrates. Metal clusters organize electron flow, while single metal ions shape active sites and lower reaction barriers.

Biogenesis and health: Metal incorporation is tightly controlled. Metallo chaperones deliver metals to apoenzymes; cellular metal availability regulates activity. Disrupted metal homeostasis can cause disease, as in Wilson disease (copper accumulation) and Menkes disease (copper deficiency).

Research and applications: Metalloproteins are studied by spectroscopy, crystallography, and computational methods to reveal metal coordination, ligation, and mechanism. They are targets for drug design and serve in biocatalysis and biosensing.