Active site rearrangement and structural divergence in prokaryotic respiratory oxidases

Science. 2019 Oct 4;366(6461):100-104. doi: 10.1126/science.aay0967.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Catalytic Domain
  • Cryoelectron Microscopy
  • Cytochrome b Group / chemistry*
  • Electron Transport Chain Complex Proteins / chemistry*
  • Escherichia coli / enzymology*
  • Escherichia coli Proteins / chemistry*
  • Heme / chemistry
  • Models, Molecular
  • Oxidation-Reduction
  • Oxidoreductases / chemistry*
  • Oxygen / chemistry
  • Protein Structure, Quaternary
  • Protein Subunits / chemistry
  • Protons
  • Ubiquinone / chemistry

Substances

  • Cytochrome b Group
  • Electron Transport Chain Complex Proteins
  • Escherichia coli Proteins
  • Protein Subunits
  • Protons
  • Ubiquinone
  • Heme
  • ubiquinone 8
  • Oxidoreductases
  • cytochrome bd terminal oxidase complex, E coli
  • Oxygen