metalloenzyme

Metalloenzyme is an enzyme that requires a metal ion for catalytic activity. In metalloenzymes, the metal is typically bound at the active site and participates directly in transforming substrates. The metal may act as a Lewis acid to polarize bonds, stabilize reaction intermediates, or participate in electron transfer. It may be a single ion, part of a metal-containing cofactor, or housed within an organometallic cluster such as an iron-sulfur cluster or molybdenum cofactor.

Common metal cofactors include iron, zinc, copper, manganese, nickel, molybdenum, and tungsten. Some enzymes contain iron-sulfur clusters or heme groups that facilitate electron transfer. Others use zinc as a Lewis acid to activate substrates. Metalloenzyme terminology emphasizes a catalytic role for the metal, whereas some metalloproteins store or stabilize metals not directly used in catalysis.

Notable examples include carbonic anhydrase (Zn2+); superoxide dismutases (Cu/Zn, Mn, or Fe); cytochrome c oxidase (Cu and Fe centers); nitrogenase (iron-molybdenum cofactor); hydrogenase (nickel-iron or iron-iron clusters); and xanthine oxidase (molybdenum cofactor). Some enzymes rely on metal clusters such as [Fe4S4] for electron transfer.

Enzymatic activity depends on metal availability and proper assembly. The apoenzyme is inactive until the metal is inserted, often with metallochaperones. Cellular metal homeostasis controls uptake, storage, and delivery to metalloenzymes to prevent deficiency or toxicity.

Disruption of metalloenzyme function can cause disease and is a focus of medical research. Metalloenzymes are also important in industry and biotechnology, including drug design and engineering of metal centers for catalysis.