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

Research output: Contribution to journalArticle

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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Catalytic Domain
Oxidoreductases
Oxygen
Electron Transport Complex IV
Cytochromes
Cryoelectron Microscopy
Water
Electron Transport
Heme
Protons
Binding Sites
Escherichia coli
Bacteria
Pharmaceutical Preparations

ASJC Scopus subject areas

  • General

Cite this

Safarian, S., Hahn, A., Mills, D. J., Radloff, M., Eisinger, M. L., Nikolaev, A., ... 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

Active site rearrangement and structural divergence in prokaryotic respiratory oxidases. / 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.

In: Science, Vol. 366, No. 6461, 04.10.2019, p. 100-104.

Research output: Contribution to journalArticle

Safarian, S, Hahn, A, Mills, DJ, Radloff, M, Eisinger, ML, Nikolaev, A, Meier-Credo, J, Melin, F, Miyoshi, H, Gennis, RB, Sakamoto, J, Langer, JD, Hellwig, P, Kühlbrandt, W & Michel, H 2019, 'Active site rearrangement and structural divergence in prokaryotic respiratory oxidases', Science, vol. 366, no. 6461, pp. 100-104. https://doi.org/10.1126/science.aay0967
Safarian S, Hahn A, Mills DJ, Radloff M, Eisinger ML, Nikolaev A et al. Active site rearrangement and structural divergence in prokaryotic respiratory oxidases. Science. 2019 Oct 4;366(6461):100-104. https://doi.org/10.1126/science.aay0967
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. / Active site rearrangement and structural divergence in prokaryotic respiratory oxidases. In: Science. 2019 ; Vol. 366, No. 6461. pp. 100-104.
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