Copper Enzymes Involved in Multi-Electron Processes

In this article focused on multielectron processes in enzymes, a comprehensive overview of the families of two copper-based enzymes that reduce dioxygen to water is presented. Emphasis has been given to outline our up-to-date understanding of multicopper oxidases (MCOs) and cytochrome c oxidases (C c Os) including their critical active site coordination, i.e., the nature of the ligands (amino acid residues) and the coordination geometry, electron transfer pathway from substrates, along with mechanisms of stepwise dioxygen reduction and protonation events. MCOs include members which effect the one-electron oxidation/dehydrogenation of substrates, and others that oxidize metal ions such as iron(II) and manganese(II) ion. CcOs couple the four-electron reduction of O 2 to the membrane translocation of protons, the proton/charge gradient thus produced being coupled to cellular ATP production. Seminal publications containing key advances on X-ray crystallographic data and valuable information obtained from implementation of several spectroscopic tools that shed light on the intricacies of electron flow and “observation” of oxy-intermediates (including kinetic and thermodynamic conclusions) have been acknowledged. The discussions at the end of each sub-section also include relevant examples of synthetic (bio) inorganic model complexes which have been attributed to each enzyme.