Molecular determinants of oxygen reactivity in bacterial terminal oxidases: Functional roles of acidic residues in cytochrome bd

Terminal oxidases are essential components of aerobic respiratory chains in both prokaryotes and eukaryotes, catalyzing the final step of the electron transport chain. These membrane proteins transfer electrons from reduced electron carriers, such as cytochrome c or quinols, to the terminal electron acceptor, molecular oxygen, reducing it to water. They play a central role in aerobic respiration and energy metabolism, adapting to diverse environmental and physiological conditions in all aerobic organisms. The cytochrome bd superfamily is found exclusively in prokaryotes. These oxidases play key roles in protection against oxidative stress, virulence, adaptability, and antibiotic resistance. Recent structural, electrochemical, and spectroscopic studies have provided new insights into oxygen reduction and coupled protonation processes and revealed a high degree of variability among members of the cytochrome bd oxidase family. Notably, an unusually high number of conserved acidic residues lie in close proximity, within 7 A of the three hemes and along the proton-transfer pathways to the active site. The recent data on the role of residues Glu445, Asp105, Asp58, and Glu99 (E. coli, bd-I numbering) in electron transfer and proton uptake are reviewed and compared within the cytochrome bd family. Structural, electrochemical, and infrared spectroscopic studies are presented.