Snapshot of an oxygen intermediate in the catalytic reaction of cytochrome c oxidase

Proc Natl Acad Sci U S A. 2019 Feb 26;116(9):3572-3577. doi: 10.1073/pnas.1814526116. Epub 2019 Feb 11.


Cytochrome c oxidase (CcO) reduces dioxygen to water and harnesses the chemical energy to drive proton translocation across the inner mitochondrial membrane by an unresolved mechanism. By using time-resolved serial femtosecond crystallography, we identified a key oxygen intermediate of bovine CcO. It is assigned to the PR-intermediate, which is characterized by specific redox states of the metal centers and a distinct protein conformation. The heme a3 iron atom is in a ferryl (Fe4+ = O2-) configuration, and heme a and CuB are oxidized while CuA is reduced. A Helix-X segment is poised in an open conformational state; the heme a farnesyl sidechain is H-bonded to S382, and loop-I-II adopts a distinct structure. These data offer insights into the mechanism by which the oxygen chemistry is coupled to unidirectional proton translocation.

Keywords: X-ray free electron laser; bioenergetics; catalytic intermediates; complex IV; crystallography.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Catalysis
  • Catalytic Domain
  • Cattle
  • Copper / chemistry
  • Crystallography, X-Ray
  • Electron Transport Complex IV / chemistry*
  • Electron Transport Complex IV / genetics
  • Heme / chemistry*
  • Iron / chemistry*
  • Oxidation-Reduction
  • Oxygen / chemistry*
  • Protein Conformation


  • Heme
  • Copper
  • Iron
  • Electron Transport Complex IV
  • Oxygen

Associated data

  • PDB/6NKN
  • PDB/6NMF
  • PDB/6NMP