Uncovering the mysteries of bacterial cytochrome c oxidases: A review on structural and molecular insights for potential application

Abstract

Cytochrome c oxidases are hemoproteins with a heme prosthetic group bound to the apoprotein. These complex enzymes are found embedded in the plasma membrane of the bacterial cells and play a vital role in the transfer of electrons from the electron transport chain to the oxygen molecule that acts as a terminal electron acceptor and gets reduced to water molecules. It helps establish a proton gradient across the plasma membrane by pumping hydrogen ions into the periplasmic space, generating adenosine triphosphate through oxidative phosphorylation. Bacteria have various cytochrome c oxidases based on the ecological niche that are differentially expressed with varying environmental conditions. Cytochrome c oxidases are made of different subunits with a distinct heme‑copper binuclear active site that catalyzes oxygen molecule reduction. Since these complex enzymes play a vital role in cellular respiration, the structure of cytochrome c oxidases remains conserved in many of the bacteria. Therefore, a detailed analysis of the structure of enzyme subunits, amino acid composition, and catalytic activity helps to design small molecules as drugs of clinical relevance for bacteria. The present review focuses on the structural details and molecular mechanisms such as proton pumping, electron transfer and the catalytic activity of oxygen reduction.