Active site rearrangement and structural divergence in prokaryotic respiratory oxidases

S. Safarian, A. Hahn, D. J. Mills, M. Radloff, M. L. Eisinger, A. Nikolaev, J. Meier-Credo, F. Melin, H. Miyoshi, R. B. Gennis, J. Sakamoto, J. D. Langer, P. Hellwig, W. Kühlbrandt, H. Michel

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Abstract

Cytochrome bd–type quinol oxidases catalyze the reduction of molecular oxygen to water in the respiratory chain of many human-pathogenic bacteria. They are structurally unrelated to mitochondrial cytochrome c oxidases and are therefore a prime target for the development of antimicrobial drugs. We determined the structure of the Escherichia coli cytochrome bd-I oxidase by single-particle cryo–electron microscopy to a resolution of 2.7 angstroms. Our structure contains a previously unknown accessory subunit CydH, the L-subfamily–specific Q-loop domain, a structural ubiquinone-8 cofactor, an active-site density interpreted as dioxygen, distinct water-filled proton channels, and an oxygen-conducting pathway. Comparison with another cytochrome bd oxidase reveals structural divergence in the family, including rearrangement of high-spin hemes and conformational adaption of a transmembrane helix to generate a distinct oxygen-binding site.

Original languageEnglish (US)
Pages (from-to)100-104
Number of pages5
JournalScience
Volume366
Issue number6461
DOIs
StatePublished - Oct 4 2019

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Cite this

Safarian, S., Hahn, A., Mills, D. J., Radloff, M., Eisinger, M. L., Nikolaev, A., Meier-Credo, J., Melin, F., Miyoshi, H., Gennis, R. B., Sakamoto, J., Langer, J. D., Hellwig, P., Kühlbrandt, W., & Michel, H. (2019). Active site rearrangement and structural divergence in prokaryotic respiratory oxidases. Science, 366(6461), 100-104. https://doi.org/10.1126/science.aay0967