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

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

Author information

1
Department of Physiology and Biophysics, Albert Einstein College of Medicine, Bronx, NY 10461.
2
Biodesign Center for Applied Structural Discovery, The Biodesign Institute, Arizona State University, Tempe, AZ 85287.
3
School of Molecular Sciences, Arizona State University, Tempe, AZ 85287.
4
Institute for X-Ray Physics, University of Goettingen, 37077 Goettingen, Germany.
5
Department of Physics, Arizona State University, Tempe, AZ 85287.
6
Hauptman-Woodward Institute and SUNY University of Buffalo, Buffalo, NY 14203.
7
SLAC National Accelerator Laboratory, Menlo Park, CA 94025.
8
Department of Physiology and Biophysics, Albert Einstein College of Medicine, Bronx, NY 10461; denis.rousseau@einstein.yu.edu.

Abstract

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 a 3 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

PMID:
30808749
PMCID:
PMC6397517
DOI:
10.1073/pnas.1814526116
[Indexed for MEDLINE]
Free PMC Article

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