Understanding the choice of copper by heme-copper oxidase using biosynthetic models in myoglobin

Heme-copper oxidases (HCOs) are key metalloenzymes in biosystems, responsible for the reduction of O₂ to H₂O using a heme-Cu_B dinuclear center. Meanwhile, the reason behind the choice of copper for the nonheme metal center remains unclear. This article highlights a recent report by Lu and co-workers, which provides strong evidence for the preference of copper over iron for the nonheme metal center, resolving a long-standing question that puzzled researchers for decades.