Homologous bd oxidases share the same architecture but differ in mechanism

• Published in: Nature communications 2019-11, Vol.10 (1), p.5138-7, Article 5138
• Main Authors: Theßeling, Alexander, Rasmussen, Tim, Burschel, Sabrina, Wohlwend, Daniel, Kägi, Jan, Müller, Rolf, Böttcher, Bettina, Friedrich, Thorsten
• Format: Article
• Language: English
• Subjects: 101/28; 101/58; 631/326/22/1290; 631/45/173; 631/535/1258/1259; 82/16; Architecture; Coenzyme Q8; Cofactors; Cytochrome; Cytochrome b Group - chemistry; Cytochrome b Group - metabolism; Cytochrome b Group - ultrastructure; Cytochrome bd; Cytochromes; E coli; Electron microscopy; Electron Transport Chain Complex Proteins - chemistry; Electron Transport Chain Complex Proteins - metabolism; Electron Transport Chain Complex Proteins - ultrastructure; Enzymes; Escherichia coli; Escherichia coli - enzymology; Escherichia coli Proteins - chemistry; Escherichia coli Proteins - metabolism; Escherichia coli Proteins - ultrastructure; Geobacillus - enzymology; Heme; Heme - chemistry; Heme - metabolism; Homology; Humanities and Social Sciences; Models, Molecular; multidisciplinary; Oxidation; Oxidoreductases - chemistry; Oxidoreductases - metabolism; Oxidoreductases - ultrastructure; Oxygen - metabolism; Protonmotive force; Protons; Reductases; Science; Science (multidisciplinary); Sequence Homology, Amino Acid; Substrate Specificity; Ubiquinol; Ubiquinone; Ubiquinone - chemistry; Ubiquinone - metabolism; Water
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-019-13122-4

Cytochrome bd oxidases are terminal reductases of bacterial and archaeal respiratory chains. The enzyme couples the oxidation of ubiquinol or menaquinol with the reduction of dioxygen to water, thus contributing to the generation of the protonmotive force. Here, we determine the structure of the Escherichia coli bd oxidase treated with the specific inhibitor aurachin by cryo-electron microscopy (cryo-EM). The major subunits CydA and CydB are related by a pseudo two fold symmetry. The heme b and d cofactors are found in CydA, while ubiquinone-8 is bound at the homologous positions in CydB to stabilize its structure. The architecture of the E. coli enzyme is highly similar to that of Geobacillus thermodenitrificans , however, the positions of heme b 595 and d are interchanged, and a common oxygen channel is blocked by a fourth subunit and substituted by a more narrow, alternative channel. Thus, with the same overall fold, the homologous enzymes exhibit a different mechanism. Cytochrome bd oxidases couple quinol oxidation and the release of protons to the periplasmic side with proton uptake from the cytoplasmic side to reduce dioxygen to water and they are the terminal reductases in bacterial and archaeal respiratory chains. Here the authors present the cryo-EM structure of Escherichia coli bd oxidase and discuss mechanistic implications.