Abstract
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 b595 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.
Highlights
Cytochrome bd oxidases are terminal reductases of bacterial and archaeal respiratory chains
The structure of the E. coli bd oxidase in the presence of the specific inhibitor aurachin C was obtained at 3.3 Å resolution by cryo-electron microscopy (cryo-EM)
The bd oxidases from E. coli and G. thermodenitrificans are homologous enzymes (Supplementary Fig. 4) and adopt a highly similar architecture (Fig. 2)
Summary
Cytochrome bd oxidases are terminal reductases of bacterial and archaeal respiratory chains. Membrane-integrated oxidases use dioxygen as terminal electron acceptor[4,5] They include the family of cytochrome bd oxidases that are terminal reductases of bacterial and archaeal respiratory chains[4,5]. The bd oxidases contribute to the pmf by a vectorial charge transfer[4,5] They display a high affinity toward dioxygen enabling growth under micro-aerobic conditions. CydA contains a soluble, periplasmic domain, the Qloop that varies in length leading to a “long” Q-loop (e.g., in E. coli) or a “short” Q-loop (e.g., in Geobacillus thermodenitrificans). This domain is expected to be involved in quinone binding and oxidation[5,11,12]. Our results suggest a different mechanism of the homologous enzymes and might provide important indications on the development of new antimicrobials that target the bd oxidase of pathogens such as Mycobacteria[14,15]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
