molybdoenzymes

Molybdoenzymes are enzymes that require a molybdenum-containing cofactor, the molybdenum cofactor (Moco), for catalytic activity. The active site generally centers on a molybdenum atom coordinated to a molybdopterin ligand, sometimes with additional sulfur or oxygen ligands. This arrangement enables two-electron redox chemistry essential for diverse oxidation and reduction reactions. In apoenzymes without the cofactor, activity is absent.

Moco biosynthesis occurs in all domains of life and entails formation of the molybdopterin platform, insertion of molybdate, and, in many enzymes, subsequent sulfuration. Once matured, the cofactor is inserted into apoproteins by specialized assembly pathways. Moieties can participate in multiple oxidation states during catalysis, often coupling substrate turnover to electron transfer to physiological electron carriers.

Molybdoenzymes participate in key global processes, including the cycles of nitrogen, sulfur, and carbon, as well as detoxification pathways. Nitrate reductases reduce nitrate to nitrite in bacteria, archaea, and plants (assimilatory and dissimilatory forms). Sulfite oxidases catalyze the oxidation of sulfite to sulfate. The xanthine oxidoreductase family, which includes xanthine oxidase and xanthine dehydrogenase, metabolizes purines and various aldehydes. Aldehyde oxidases, formate dehydrogenases, and other Mo-containing enzymes play roles in drug metabolism and xenobiotic processing.

In humans, proper MoCo function is essential; defects in MoCo biosynthesis or insertion cause molybdenum cofactor deficiency, a severe, often fatal disorder with neurological and developmental consequences. Understanding molybdoenzymes informs areas from nutrition and metabolism to environmental biology and medicine.