Molybdenum‐Copper Antagonism In Metalloenzymes And Anti‐Copper Therapy

Abstract The connection between 3d (Cu) and 4d (Mo) via the “Mo−S−Cu” unit is called Mo−Cu antagonism. Biology offers case studies of such interactions in metalloproteins such as Mo/Cu−CO Dehydrogenases (Mo/Cu−CODH), and Mo/Cu Orange Protein (Mo/Cu−ORP). The CODH significantly maintains the CO level in the atmosphere below the toxic level by converting it to non–toxic CO 2 for respiring organisms. Several models were synthesized to understand the structure–function relationship of these native enzymes. However, this interaction was first observed in ruminants, and they convert molybdate (MoO 4 2− ) into tetrathiomolybdate (MoS 4 2− ; TTM), reacting with cellular Cu to yield biological unavailable Mo/S/Cu cluster, then developing Cu‐deficiency diseases. These findings inspire the use of TTM as a Cu‐sequester drug, especially for treating Cu‐dependent human diseases such as Wilson diseases (WD) and cancer. It is well known that a balanced Cu homeostasis is essential for a wide range of biological processes, but negative consequence leads to cell toxicity. Therefore, this review aims to connect the Mo−Cu antagonism in metalloproteins and anti‐copper therapy.