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 CO2 for respiring organisms. Several model studies were synthesized to understand the structure‐function relationship of these native enzymes. However, this interaction was first observed in ruminants, and they convert molybdate (MoO42–) into tetrathiomolybdate (MoS42–; 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.